Oxazolidinone antibacterial agents having a thiocarbonyl functionality

ABSTRACT

The present invention provides compounds of Formula 1  
                 
 
     or pharmaceutical acceptable salts thereof wherein A, G and R 1  are as defined in the claims which are antibacterial agents.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of co-pendingapplication U.S. Ser. No. 09/080,751, filed May 18, 1998, which claimsthe benefit of provisional application U.S. Ser. No. 60/048,342, filedMay 30, 1997, under 35 USC 119(e)(i).

BACKGROUND OF THE INVENTION

[0002] The present invention relates to new and useful oxazolidinonecompounds and their preparations, and more particularly to oxazolidinonecompounds in which the carbonyl functionality of —NH—C(O)—R is convertedto a thiocarbonyl functionality, such as a thiourea —NH—C(S)—NH₂, analkyl thiourea —NH—C(S)—NH—(C₁₋₄ alkyl), thioamide —NH—C(S)—(C₁₋₄ alkyl)or —NH—C(S)—H.

[0003] Replacement of the oxygen atom with a sulfur atom hasunexpectedly improved the antimicrobial properties of the compounds. Thecompounds are useful antimicrobial agents, effective against a number ofhuman and veterinary pathogens, including Gram-positive aerobic bacteriasuch as multiply-resistant staphylococci and streptococci, Gram-negativeorganisms such as H. influenzae and M. catarrahlis as well as anaerobicorganisms such as bacteroides and clostridia species, and acid-fastorganisms such as Mycobacterium tuberculosis and Mycobacterium avium.The compounds are particularly useful because they are effective againstthe latter organisms which are known to be responsible for infection inpersons with AIDS.

SUMMARY OF THE INVENTION

[0004] In one aspect the subject invention is a compound of the FormulaI

[0005] or pharmaceutical acceptable salts thereof wherein:

[0006] G is

[0007] R₁ is

[0008] a) H,

[0009] b) NH₂,

[0010] c) NH—C₁₋₄ alkyl,

[0011] d) C₁₋₄ alkyl,

[0012] e) —OC₁₋₄ alkyl,

[0013] f) —S C₁₋₄ alkyl,

[0014] g) C₁₋₄ alkyl substituted with 1-3 F, 1-2 Cl, CN or —COOC₁₋₄alkyl,

[0015] h) C₃₋₆ cycloalkyl,

[0016] i) N(C₁₋₄ alkyl)₂ or

[0017] j) N(CH₂)₂₋₅;

[0018] A is

[0019] d) a 5-membered heteroaromatic moiety having one to three atomsselected from the group consisting of S, N, and O,

[0020] wherein the 5-membered heteroaromatic moiety is bonded via acarbon atom,

[0021] wherein the 5-membered heteroaromatic moiety can additionallyhave a fused-on benzene or naphthyl ring,

[0022] wherein the heteroaromatic moiety is optionally substituted withone to three R₄₈,

[0023] e) a 6-membered heteroaromatic moiety having at least onenitrogen atom,

[0024] wherein the heteroaromatic moiety is bonded via a carbon atom,

[0025] wherein the 6-membered heteroaromatic moiety can additionallyhave a fused-on benzene or naphthyl ring,

[0026] wherein the heteroaromatic moiety is optionally substituted withone to three R₅₅,

[0027] f) a β-carbolin-3-yl, or indolizinyl bonded via the 6-memberedring, optionally substituted with one to three R₅₅,

[0028] wherein R₂ is

[0029] a) H,

[0030] b) F,

[0031] c) Cl,

[0032] d) Br,

[0033] e) C₁₋₃ alkyl,

[0034] f) NO₂, or

[0035] g) R₂ and R₃ taken together are —O—(CH₂)_(h)—O—;

[0036] R₃ is

[0037] a) —S(═O)_(i) R₄,

[0038] b) —S(═O)₂—N═S(O)_(j)R₅R₆,

[0039] c) —SC(═O)R₇,

[0040] d) —C(═O)R₈,

[0041] e) —C(═O)R₉,

[0042] f) —C(═O)NR₁₀R₁₁,

[0043] g) —C(═NR₁₂)R₈,

[0044] h) —C(R₈)(R₁₁)—OR₁₃,

[0045] i) —C(R₉)(R₁₁)—OR₁₃,

[0046] j) —C(R₈)(R₁₁)—OC(═O)R₁₃,

[0047] k) —C(R₉)(R₁₁)—OC(═O)R₁₃,

[0048] l) —NR₁₀R₁₁,

[0049] m) —N(R₁₀)—C(═O)R₇,

[0050] n) —N(R₁₀)—S(═O)_(i)R₇,

[0051] o) —C(OR₁₄)(OR₁₅)R₈,

[0052] p) —C(R₈)(R₁₆)—NR₁₀R₁₁, or

[0053] q) C₁₋₈ alkyl substituted with one or more ═O other than at alphaposition, —S(═O)_(i)R₁₇, —NR₁₀R₁₁, C₂₋₅ alkenyl, or C₂₋₅ alkynyl;

[0054] R₄ is

[0055] a) C₁₋₄ alkyl optionally substituted with one or more halos, OH,CN, NR₁₀R₁₁, or —CO₂R₁₃,

[0056] b) C₂₋₄ alkenyl,

[0057] c) —NR₁₆R₁₈,

[0058] d) —N₃,

[0059] e) —NHC(═O)R₇,

[0060] f) —NR₂₀C(═O)R₇,

[0061] g) —N(R₁₉)₂,

[0062] h) —NR₁₆R₁₉, or

[0063] i) —NR₁₉R₂₀,

[0064] R₅ and R₆ at each occurrence are the same or different and are

[0065] a) C₁₋₂ alkyl, or

[0066] b) R₅ and R₆ taken together are —(CH₂)_(k)—;

[0067] R₇ is C₁₋₄ alkyl optionally substituted with one or more halos;

[0068] R₈ is

[0069] a) H, or

[0070] b) C₁₋₈ alkyl optionally substituted with one or more halos, orC₃₋₈ cycloalkyl;

[0071] R₉ is C₁₋₄ alkyl substituted with one or more

[0072] a) —S(═O)R₁₇,

[0073] b) —OR₁₃,

[0074] c) —OC(═O)R₁₃,

[0075] d) —NR₁₀R₁₁, or

[0076] e) C₁₋₅ alkenyl optionally substituted with CHO;

[0077] R₁₀ and R₁₁ at each occurrence are the same or different and are

[0078] a) H,

[0079] b) C₁₋₄ alkyl, or

[0080] c) C₃₋₈ cycloalkyl;

[0081] R₁₂ is

[0082] a) —NR₁₀R₁₁,

[0083] b) —OR₁₀; or

[0084] c) —NHC(═O)R₁₀;

[0085] R₁₃ is

[0086] a) H, or

[0087] b) C₁₋₄ alkyl;

[0088] R₁₄ and R₁₅ at each occurrence are the same or different and are

[0089] a) C₁₋₄ alkyl, or

[0090] b) R₁₄ and R₁₅ taken together are —(CH)_(l)—;

[0091] R₁₆ is

[0092] a) H,

[0093] b) C₁₋₄ alkyl, or

[0094] c) C₃₋₈ cycloalkyl;

[0095] R₁₇ is

[0096] a) C₁₋₄ alkyl, or

[0097] b) C₃₋₈ cycloalkyl;

[0098] R₁₈ is

[0099] a) H,

[0100] b) C₁₋₄ alkyl,

[0101] c) C₂₋₄ alkenyl,

[0102] d) C₃₋₄ cycloalkyl,

[0103] e) —OR₁₋₃ or

[0104] f) —NR₂₁R₂₂;

[0105] R₁₉ is

[0106] a) Cl,

[0107] b) Br, or

[0108] c) I;

[0109] R₂₀ is a physiologically acceptable cation;

[0110] R₂₁ and R₂₂ at each occurrence are the same or different and are

[0111] a) H,

[0112] b) C₁₋₄ alkyl, or

[0113] c) —NR₂₁R₂₂ taken together are —(CH₂)_(m)—;

[0114] wherein R₂₃ and R₂₄ at each occurrence are the same or differentand are

[0115] a) H,

[0116] b) F,

[0117] c) Cl,

[0118] d) C₁₋₂ alkyl,

[0119] e) CN

[0120] f) OH,

[0121] g) C₁₋₂ alkoxy,

[0122] h) nitro, or

[0123] i) amino;

[0124] Q is

[0125] m) a diazinyl group optionally substituted with X and Y,

[0126] n) a triazinyl group optionally substituted with X and Y,

[0127] o) a quinolinyl group optionally substituted with X and Y,

[0128] p) a quinoxalinyl group optionally substituted with X and Y,

[0129] q) a naphthyridinyl group optionally substituted with X and Y,

[0130] Q and R₂₄ taken together are

[0131] wherein Z¹ is

[0132] a) —CH₂—,

[0133] b) —CH(R¹⁰⁴)—CH₂—,

[0134] c) —C(O)—, or

[0135] d) —CH₂CH₂CH₂—;

[0136] wherein Z² is

[0137] a) —O₂S—,

[0138] b) —O—,

[0139] c) —N(R¹⁰⁷)—,

[0140] d) —OS—, or

[0141] e) —S—;

[0142] wherein Z³ is

[0143] a) —O₂S—,

[0144] b) —O—,

[0145] c) —OS—, or

[0146] d) —S—;

[0147] wherein A¹ is

[0148] a) H—, or

[0149] b) CH₃;

[0150] wherein A² is

[0151] a) H—,

[0152] b) HO—,

[0153] c) CH₃—,

[0154] d) CH₃O—,

[0155] e) R¹⁰²O—CH₂—C(O)—NH—

[0156] f) R¹⁰³O—C(O)—NH—,

[0157] g) (C₁-C₂)alkyl-O—C(O)—,

[0158] h) HO—CH₂—,

[0159] i) CH₃O—NH—,

[0160] j) (C₁-C₃)alkyl-O₂C—

[0161] k) CH₃—C(O)—,

[0162] l) CH₃—C(O)—CH₂—,

[0163] A¹ and A² taken together are:

[0164]  wherein R¹⁰² is

[0165] a) H—,

[0166] b) CH₃—,

[0167] c) phenyl-CH₂—, or

[0168] d) CH₃C(O)—;

[0169]  wherein R¹⁰³ is

[0170] a) (C₁-C₃)alkyl-, or

[0171] b) phenyl-;

[0172]  wherein R¹⁰⁴ is

[0173] a) H—, or

[0174] b) HO—;

[0175]  wherein R¹⁰⁵ is

[0176] a) H—,

[0177] b) (C₁-C₃)alkyl-,

[0178] c) CH₂═CH—CH₂—, or

[0179] d) CH₃—O—(CH₂)₂—;

[0180]  wherein R¹⁰⁶ is

[0181] a) CH₃—C(O)—,

[0182] b) H—C(O)—,

[0183] c) Cl₂CH—C(O)—,

[0184] d) HOCH₂—C(O)—,

[0185] e) CH₃SO₂—,

[0186] g) F₂CHC(O)—,

[0187] i) H₃C—C(O)—O—CH₂—C(O)—,

[0188] j) H—C(O)—O—CH₂—C(O)—,

[0189] l) HC≡C—CH₂O—CH₂—C(O)—, or

[0190] m) phenyl-CH₂—O—CH₂—C(O)—;

[0191]  wherein R¹⁰⁷ is

[0192] a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—,

[0193] b) R¹⁰³O—C(O)—,

[0194] c) R¹⁰⁸—C(O)—,

[0195] f) H₃C—C(O)—(CH₂)₂—C(O)—,

[0196] g) R¹⁰⁹—SO₂—,

[0197] i) HO—CH₂—C(O)—,

[0198] j) R¹¹⁶—(CH₂)₂—,

[0199] k) R¹¹³—C(O)—O—CH₂—C(O)—,

[0200] l) (CH₃)₂N—CH₂—C(O)—NH—,

[0201] m) NC—CH₂—,

[0202] n) F₂—CH—CH₂—, or

[0203] o) R¹⁵⁰R¹⁵¹NSO₂

[0204]  wherein R¹⁰⁸ is

[0205] a) H—,

[0206] b) (C₁-C₄)alkyl,

[0207] c) aryl —(CH₂)_(p),

[0208] d) ClH₂C—,

[0209] e) Cl₂HC—,

[0210] f) FH₂C—,

[0211] g) F₂HC—,

[0212] h) (C₃-C₆)cycloalkyl, or

[0213] i) CNCH₂—.

[0214]  wherein R¹⁰⁹ is

[0215] a) alkylC₁-C₄,

[0216] b) —CH₂Cl

[0217] c) —CH₂CH═CH₂,

[0218] d) aryl, or

[0219] e) —CH₂CN;

[0220]  wherein R¹¹⁰ and R¹¹¹ are independently

[0221] a) H—,

[0222] b) CH₃—; or

[0223]  wherein R¹¹² is

[0224] a) H—,

[0225] b) CH₃O—CH₂O—CH₂—, or

[0226] c) HOCH₂—;

[0227]  wherein R¹¹³ is

[0228] a) CH₃—,

[0229] b) HOCH₂—,

[0230] c) (CH₃)₂N-phenyl, or

[0231] d) (CH₃)₂N—CH₂—;

[0232]  wherein R¹¹⁴ is

[0233] a) HO—,

[0234] b) CH₃O—,

[0235] c) H₂N—,

[0236] d) CH₃O—C(O)—O—,

[0237] e) CH₃—C(O)—O—CH₂—C(O)—O—,

[0238] f) phenyl-CH₂—O—CH₂—C(O)—O—,

[0239] g) HO—(CH₂)₂—O—,

[0240] h) CH₃O—CH₂—O—(CH₂)₂—O—, or

[0241] i) CH₃O—CH₂—;

[0242]  wherein R¹¹³ is

[0243] a) CH₃—,

[0244] b) HOCH₂—,

[0245] c) (CH₃)₂N-phenyl, or

[0246] d) (CH₃)₂N—CH₂—;

[0247]  wherein R¹¹⁵ is

[0248] a) H—, or

[0249] b) Cl—;

[0250]  wherein R¹¹⁶ is

[0251] a) HO—

[0252] b) CH₃O—, or

[0253] c) F;

[0254]  wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹taken together with the nitrogen atom to which each is attached form amonocyclic heterocyclic ring having from 3 to 6 carbon atoms;

[0255] B is an unsaturated 4-atom linker having one nitrogen and threecarbons;

[0256] M is

[0257] a) H,

[0258] b) C₁₋₈ alkyl,

[0259] c) C₃₋₈ cycloalkyl,

[0260] d) —(CH₂)_(m)OR₁₃, or

[0261] e) —(CH₂)_(h)—NR₂₁R₂₂;

[0262] Z is

[0263] a) O,

[0264] b) S, or

[0265] c) NM;

[0266] W is

[0267] a) CH,

[0268] b) N, or

[0269] c) S or O when Z is NM;

[0270] Y is

[0271] a) H,

[0272] b) F,

[0273] c) Cl,

[0274] d) Br,

[0275] e) C₁₋₃ alkyl, or

[0276] f) NO₂;

[0277] X is

[0278] a) H,

[0279] b) —CN,

[0280] c) OR₂₇,

[0281] d) halo,

[0282] e) NO₂,

[0283] f) tetrazoyl,

[0284] g) —SH,

[0285] h) —S(═O)_(i)R₄,

[0286] i) —S(═O)₂—N═S(O)_(j)R₅R₆,

[0287] j) —SC(═O)R₇,

[0288] k) —C(═O)R₂₅,

[0289] l) —C(═O)NR₂₇R₂₈,

[0290] m) —C(═NR₂₉)R₂₅,

[0291] n) —C(R₂₅)(R₂₈)—OR₁₃,

[0292] o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃,

[0293] p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈,

[0294] q) —NR₂₇R₂₈,

[0295] r) —N(R₂₇)C(═O)R₇,

[0296] s) —N(R₂₇)—S(═O)_(i)R₇,

[0297] t) —C(OR₁₄)(OR₁₅)R₂₈,

[0298] u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or

[0299] v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O otherthan at alpha position, —S(═O)_(i)R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅alkynyl, or C₃₋₈ cycloalkyl;

[0300] R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same asdefined above;

[0301] R₂₅ is

[0302] a) H,

[0303] b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇,—OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or

[0304] c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃;

[0305] R₂₆ is

[0306] a) R₂₈, or

[0307] b) NR₂₇N₂₈;

[0308] R₂₇ and R₂₈ at each occurrence are the same or different and are

[0309] a) H,

[0310] b) C₁₋₈ alkyl,

[0311] c) C₃₋₈ cycloalkyl,

[0312] d) —(CH₂)_(m)OR₁₃,

[0313] e) —(CH₂)_(h)—NR₂₁R₂₂, or

[0314] f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—,—(CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇);

[0315] R₂₉ is

[0316] a) —NR₂₇R₂₈,

[0317] b) —OR₂₇, or

[0318] c) —NHC(═O)R₂₈;

[0319] wherein R₃₀ is

[0320] a) H,

[0321] b) C₁₋₈ alkyl optionally substituted with one or more halos, or

[0322] c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆alkoxy;

[0323] wherein E is

[0324] a) NR₃₉,

[0325] b) —S(═O)_(i), or

[0326] c) O;

[0327] R₃₈ is

[0328] a) H,

[0329] b) C₁₋₆ alkyl,

[0330] c) —(CH₂)_(q)-aryl, or

[0331] d) halo;

[0332] R₃₉ is

[0333] a) H,

[0334] b) C₁₋₆ alkyl optionally substituted with one or more OH, halo,or —CN,

[0335] c) —(CH₂)_(q)-aryl,

[0336] d) —CO₂R₄₀,

[0337] e) —COR₄₁,

[0338] f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀,

[0339] g) —S(═O)₂—C₁₋₆ alkyl,

[0340] h) —S(═O)₂—(CH₂)_(q)-aryl, or

[0341] i) —(C═O)_(j)-Het;

[0342] R₄₀ is

[0343] a) H,

[0344] b) C₁₋₆ alkyl optionally substituted with one or more OH, halo,or —CN,

[0345] c) —(CH₂)_(q)-aryl, or

[0346] d) —(CH₂)_(q)—OR₄₂;

[0347] R₄₁ is

[0348] a) C₁₋₆ alkyl optionally substituted with one or more OH, halo,or —CN,

[0349] b) —(CH₂)_(q)-aryl, or

[0350] c) —(CH₂)_(q)—OR₄₂;

[0351] R₄₂ is

[0352] a) H,

[0353] b) C₁₋₆ alkyl,

[0354] c) —(CH₂)_(q)-aryl, or

[0355] d) —C(═O)—C₁₋₆ alkyl;

[0356] aryl is

[0357] a) phenyl,

[0358] b) pyridyl, or

[0359] c) napthyl; a to c optionally substituted with one or more halo,—CN, OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio;

[0360] wherein R₄₃ is

[0361] a) H,

[0362] b) C₁₋₂ alkyl,

[0363] c) F, or

[0364] d) OH;

[0365] R₄₄ is

[0366] a) H,

[0367] b) CF₃,

[0368] c) C₁₋₃ alkyl optionally substituted with one or more halo,

[0369] d) phenyl optionally substituted with one or more halo,

[0370] e) R₄₄ and R₄₅ taken together are a 5-, 6-, or 7-membered ring ofthe formula,

[0371]  or

[0372] f) R₄₄ and R₄₅ taken together are —(CH₂)_(k)—, when R₄₆ is anelectron withdrawing group;

[0373] R₄₅ and R₄₆ at each occurrence are the same or different and are

[0374] a) an electron-withdrawing group,

[0375] b) H,

[0376] c) CF₃,

[0377] d) C₁₋₃ alkyl optionally substituted with one halo,

[0378] e) phenyl, provided at least one of R₄₅ or R₄₆ is anelectron-withdrawing group, or

[0379] f) R₄₅ and R₄₆ taken together are a 5-, 6-, 7-membered ring ofthe formula

[0380] U is

[0381] a) CH₂,

[0382] b) O,

[0383] c) S, or

[0384] d) NR₄₇;

[0385] R₄₇ is

[0386] a) H, or

[0387] b) C₁₋₅ alkyl;

[0388] wherein R₄₈ is

[0389] a) carboxyl,

[0390] b) halo,

[0391] c) —CN,

[0392] d) mercapto,

[0393] e) formyl,

[0394] f) CF₃,

[0395] g) —NO₂,

[0396] h) C₁₋₆ alkoxy,

[0397] i) C₁₋₆ alkoxycarbonyl,

[0398] j) C₁₋₆ alkythio,

[0399] k) C₁₋₆ acyl,

[0400] l) —NR₄₉ R₅₀,

[0401] m) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅acyl, or —NR₄₉R₅₀,

[0402] n) C₂₋₈ alkenylphenyl optionally substituted with one or two R₅₁,

[0403] o) phenyl optionally substituted with one or two R₅₁,

[0404] p) a 5-, or 6-membered (un)saturated heterocyclic moiety havingone to three atoms selected from the group consisting of S, N, and O,optionally substituted with one or two R₅₁, or

[0405] R₄₉ and R₅₀ at each occurrence are the same or different and are

[0406] a) H,

[0407] b) C₁₋₄ alkyl,

[0408] c) C₅₋₆ cycloalkyl, or

[0409] d) R₄₉ and R₅₀ taken together with the nitrogen atom is a 5-,6-membered saturated heterocyclic moiety which optionally has a furtherhetero atom selected from the group consisting of S, N, and O, and canin turn be optionally substituted with, including on the furthernitrogen atom, C₁₋₃ alkyl, or C₁₋₃ acyl;

[0410] R₅₁ is

[0411] a) carboxyl,

[0412] b) halo,

[0413] c) —CN,

[0414] d) mercapto,

[0415] e) formyl,

[0416] f) CF₃,

[0417] g) —NO₂,

[0418] h) C₁₋₆ alkoxy,

[0419] i) C₁₋₆ alkoxycarbonyl,

[0420] j) C₁₋₆ alkythio,

[0421] k) C₁₋₆ acyl,

[0422] l) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅acyl, or —NR₄₉R₅₀,

[0423] m) phenyl,

[0424] n) —C(═O)NR₅₂ R₅₃,

[0425] o) —NR₄₉R₅₀,

[0426] p) —N(R₅₂)(—SO₂R₅₄),

[0427] q) —SO₂—NR₅₂R₅₃, or

[0428] r) —S(═O)₁R₅₄;

[0429] R₅₂ and R₅₃ at each occurrence are the same or different and are

[0430] a) H,

[0431] b) C₁₋₆ alkyl, or

[0432] c) phenyl;

[0433] R₅₄ is

[0434] a) C₁₋₄ alkyl, or

[0435] b) phenyl optionally substituted with C₁₋₄ alkyl;

[0436] wherein R₅₅ is

[0437] a) carboxyl,

[0438] b) halo,

[0439] c) —CN,

[0440] d) mercapto,

[0441] e) formyl,

[0442] f) CF₃,

[0443] g) —NO₂,

[0444] h) C₁₋₆ alkoxy,

[0445] i) C₁₋₆ alkoxycarbonyl,

[0446] j) C₁₋₆ alkythio

[0447] k) C₁₋₆ acyl,

[0448] l) —NR₅₆ R₅₇,

[0449] m) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅acyl, or —NR₅₆R₅₇,

[0450] n) C₂₋₈ alkenylphenyl optionally substituted with one or two R₅₈,

[0451] o) phenyl optionally substituted with one or two R₅₈,

[0452] p) a 5- or 6-membered (un)saturated heterocyclic moiety havingone to three atoms selected from the group consisting of S, N, and O,optionally substituted with one or two R₅₈, or

[0453] R₅₆ and R₅₇ at each occurrence are the same or different and are

[0454] a) H,

[0455] b) formyl,

[0456] c) C₁₋₄ alkyl,

[0457] d) C₁₋₄ acyl,

[0458] e) phenyl,

[0459] f) C₃₋₆ cycloalkyl, or

[0460] g) R₅₆ and R₅₇ taken together with the nitrogen atom is a 5-,6-membered saturated heterocyclic moiety which optionally has a furtherhetero atom selected from the group consisting of S, N, and O, and canin turn be optionally substituted with, including on the furthernitrogen atom, phenyl, pyrimidyl, C₁₋₃ alkyl, or C₁₋₃ acyl;

[0461] R₅₈ is

[0462] a) carboxyl,

[0463] b) halo,

[0464] c) —CN,

[0465] d) mercapto,

[0466] e) formyl,

[0467] f) CF₃,

[0468] g) —NO₂,

[0469] h) C₁₋₆ alkoxy,

[0470] i) C₁₋₆ alkoxycarbonyl,

[0471] j) C₁₋₆ alkythio,

[0472] k) C₁₋₆ acyl,

[0473] l) phenyl,

[0474] m) C₁₋₆ alkyl optionally substituted with OH, azido, C₁₋₅ alkoxy,C₁₋₅ acyl, —NR₆₅R₆₆, —SR₆₇, —O—SO₂R₆₈, or

[0475] n) —C(═O)NR₅₉ R₆₀,

[0476] o) —NR₅₆R₅₇,

[0477] p) —N(R₅₉)(—SO₂R₅₄),

[0478] q) —SO₂—NR₅₉R₆₀,

[0479] r) —S(═O)_(i)R₅₄,

[0480] s) —CH═N—R₆₁, or

[0481] t) —CH(OH)—SO₃R₆₄;

[0482] R₅₄ is the same as defined above;

[0483] R₅₉ and R₆₀ at each occurrence are the same or different and are

[0484] a) H,

[0485] b) C₁₋₆ alkyl,

[0486] c) phenyl, or

[0487] d) tolyl;

[0488] R₆₁ is

[0489] a) OH,

[0490] b) benzyloxy,

[0491] c) —NH—C(═O)—NH₂,

[0492] d) —NH—C(═S)—NH₂, or

[0493] e) —NH—C(═NH)—NR₆₂R₆₃;

[0494] R₆₂ and R₆₃ at each occurrence are the same or different and are

[0495] a) H, or

[0496] b) C₁₋₄ alkyl optionally substituted with phenyl or pyridyl;

[0497] R₆₄ is

[0498] a) H, or

[0499] b) a sodium ion;

[0500] R₆₅and R₆₆ at each occurrence are the same or different and are

[0501] a) H,

[0502] b) formyl,

[0503] c) C₁₋₄ alkyl,

[0504] d) C₁₋₄ acyl,

[0505] e) phenyl,

[0506] f) C₃₋₆ cycloalkyl,

[0507] g) R₆₅ and R₆₆ taken together are a 5-, 6-membered saturatedheterocyclic moiety having one to three atoms selected from the groupconsisting of S, N, and O, optionally substituted with, including on thenitrogen atom, phenyl, pyrimidyl, C₁₋₃ alkyl, or C₁₋₃ acyl,

[0508] h) —P(O)(OR₇₀)(OR₇₁), or

[0509] i) —SO₂—R₇₂;

[0510] R₆₇ is

[0511] R₆₈ is C₁₋₃ alkyl;

[0512] R₆₉ is

[0513] a) C₁₋₆ alkoxycarbonyl, or

[0514] b) carboxyl;

[0515] R₇₀ and R₇₁ at each occurrence are the same or different and are

[0516] a) H, or

[0517] b) C₁₋₃ alkyl;

[0518] R₇₂ is

[0519] a) methyl,

[0520] b) phenyl, or

[0521] c) tolyl;

[0522] wherein K is

[0523] a) O, or

[0524] b) S;

[0525] R₇₃, R₇₄, R₇₅, R₇₆, and R₇₇ at each occurrence are the same ordifferent and are

[0526] a) H,

[0527] b) carboxyl,

[0528] c) halo,

[0529] d) —CN,

[0530] e) mercapto,

[0531] f) formyl,

[0532] g) CF₃,

[0533] h) —NO₂,

[0534] i) C₁₋₆ alkoxy,

[0535] j) C₁₋₆ alkoxycarbonyl,

[0536] k) C₁₋₆ alkythio,

[0537] l) C₁₋₆ acyl,

[0538] m) —NR₇₈ R₇₉,

[0539] n) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅acyl, —NR₇₈R₇₉, —N(phenyl)(CH₂—CH₂—OH), —O—CH(CH₃)(OCH₂CH₃), or—O-phenyl-[para-NHC(═O)CH₃],

[0540] o) C₂₋₈ alkenylphenyl optionally substituted with R₅₁,

[0541] p) phenyl optionally substituted with R₅₁, or

[0542] q) a 5-, or 6-membered (un)saturated heterocyclic moiety havingone to three atoms selected from the group consisting of S, N, and O,optionally substituted with R₅₁;

[0543] R₅₁ is the same as defined above;

[0544] R₇₈ and R₇₉ at each occurrence are the same or different and are

[0545] a) H,

[0546] b) C₁₋₄ alkyl,

[0547] c) phenyl, or

[0548] d) R₇₈ and R₇₉ taken together with the nitrogen atom is a 5-,6-membered saturated heterocyclic moiety which optionally has a furtherhetero atom selected from the group consisting of S, N, and O, and canin turn be optionally substituted with, including on the furthernitrogen atom, C₁₋₃ alkyl, or C₁₋₃ acyl;

[0549] wherein T is

[0550] a) O,

[0551] b) S, or

[0552] c) SO₂;

[0553] R₇₅, R₇₆, and R₇₇ are the same as defined above;

[0554] R₈₀ is

[0555] a) H,

[0556] b) formyl,

[0557] c) carboxyl,

[0558] d) C₁₋₆ alkoxycarbonyl,

[0559] e) C₁₋₈ alkyl,

[0560] f) C₂₋₈ alkenyl,

[0561]  wherein the substituents (e) and (f) can be optionallysubstituted with OH, halo, C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio orC₁₋₆ alkoxycarbonyl, or phenyl optionally substituted with halo,

[0562] g) an aromatic moiety having 6 to 10 carbon atoms optionallysubstituted with carboxyl, halo, —CN, formyl, CF₃, —NO₂, C₁₋₆ alkyl,C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio, or C₁₋₆ alkoxycarbonyl;

[0563] h) —NR₈₁R₈₂,

[0564] i) —OR₉₀,

[0565] j) —S(═O)_(i)—R₉₁,

[0566] k) —SO₂—N(R₉₂)(R₉₃), or

[0567] l) a radical of the following formulas:

[0568] R₈₁ and R₈₂ at each occurrence are the same or different and are

[0569] a) H,

[0570] b) C₃₋₆ cycloalkyl,

[0571] c) phenyl,

[0572] d) C₁₋₆ acyl,

[0573] e) C₁₋₈ alkyl optionally substituted with OH, C₁₋₆ alkoxy whichcan be substituted with OH, a 5-, or 6-membered aromatic heterocyclicmoiety having one to three atoms selected from the group consisting ofS, N, and O, phenyl optionally substituted with OH, CF₃, halo, —NO₂,C₁₋₄ alkoxy, —NR₈₃R₈₄, or

[0574] V is

[0575] a) O,

[0576] b) CH₂, or

[0577] c) NR₈₇;

[0578] R₈₃ and R₈₄ at each occurrence are the same or different and are

[0579] a) H, or

[0580] b) C₁₋₄ alkyl;

[0581] R₈₅ is

[0582] a) OH,

[0583] b) C₁₋₄ alkoxy, or

[0584] c) —NR₈₈ R₈₉;

[0585] R₈₆ is

[0586] a) H, or

[0587] b) C₁₋₇ alkyl optionally substituted with indolyl, OH, mercaptyl,imidazoly, methylthio, amino, phenyl optionally substituted with OH,—C(═O)—NH₂, —CO₂H, or —C(═NH)—NH₂;

[0588] R₈₇ is

[0589] a) H,

[0590] b) phenyl, or

[0591] c) C₁₋₆ alkyl optionally substituted by OH;

[0592] R₈₈ and R₈₉ at each occurrence are the same or different and are

[0593] a) H,

[0594] b) C₁₋₅ alkyl

[0595] c) C₃₋₆ cycloalky, or

[0596] d) phenyl;

[0597] R₉₀ is

[0598] a) C₁₋₈ alkyl optionally substituted with C₁₋₆ alkoxy or C₁₋₆hydroxy, C₃₋₆ cycloalkyl, a 6-membered aromatic optionally benzo-fusedheterocyclic moiety having one to three nitrogen atoms, which can inturn be substituted with one or two —NO₂, CF₃, halo, —CN, OH, C₁₋₅alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl;

[0599] c) phenyl, or

[0600] d) pyridyl;

[0601] R₉₁ is

[0602] a) C₁₋₁₆ alkyl,

[0603] b) C₂₋₁₆ alkenyl,

[0604]  wherein the substituents (a) and (b) can be optionallysubstituted with C₁₋₆ alkoxycarbonyl, or a 5-, 6-, 7-membered aromaticheterocyclic moiety having one to three atoms selected from the groupconsisting of S, N, and O,

[0605] c) an aromatic moiety having 6 to 10 carbon atoms, or

[0606] d) a 5-, 6-, 7-membered aromatic heterocyclic moiety having oneto three atoms selected from the group consisting of S, N, and O,

[0607]  wherein the substituents (c) and (d) can be optionallysubstituted with carboxyl, halo, —CN, formyl, CF₃, —NO₂, C₁₋₆ alkyl,C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio, or C₁₋₆ alkoxycarbonyl;

[0608] R₉₂ and R₉₃ at each occurrence are the same or different and are

[0609] a) H,

[0610] b) phenyl,

[0611] c) C₁₋₆ alkyl, or

[0612] d) benzyl;

[0613] R₉₄ and R₉₅ at each occurrence are the same or different and are

[0614] a) H,

[0615] b) OH,

[0616] c) C₁₋₆ alkyl optionally substituted with —NR₈₃ R₈₄, or

[0617] d) R₉₄ and R₉₅ taken together are ═O;

[0618] R₉₆ is

[0619] a) an aromatic moiety having 6 to 10 carbon atoms,

[0620] b) a 5-, or 6-membered aromatic optionally benzo-fusedheterocyclic moiety having one to three atoms selected from the groupconsisting of S, N, and O,

[0621]  wherein the substituents (a) and (b) which can in turn besubstituted with one or three —NO₂, CF₃, halo, —CN, OH, phenyl, C₁₋₅alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl,

[0622] c) morpholinyl,

[0623] d) OH,

[0624] e) C₁₋₆ alkoxy,

[0625] f) —NR₈₃R₈₄,

[0626] g) —C(═O)—R₉₇, or

[0627] R₉₇ is

[0628] a) morpholinyl,

[0629] b) OH, or

[0630] c) C₁₋₆ alkoxy;

[0631] h is 1, 2, or 3;

[0632] i is 0, 1, or 2;

[0633] j is 0 or 1;

[0634] k is 3, 4, or 5;

[0635] l is 2 or 3;

[0636] m is 4 or 5;

[0637] n is 0, 1, 2, 3, 4, or 5;

[0638] p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p togetherare 1, 2, 3, 4, or 5;

[0639] q is 1, 2, 3, or 4;

[0640] r is 2, 3, or 4;

[0641] t is 0, 1, 2, 3, 4, 5, or 6;

[0642] u is 1 or 2;

[0643] w is 0, 1, 2, or 3.

DETAILED DESCRIPTION OF THE INVENTION

[0644] The new compounds of the invention can be prepared using knowncompounds and intermediates of oxazolidinones, isoxazolines andbutyolactones as intermediates and synthetic methods known in the art.Thioamides of the invention can typically be prepared by the reaction ofthe corresponding amide with Lawesson's reagent.

[0645] Compounds disclosed in the following publications are suitableintermediates for preparation of the compounds of this invention and arehereby incorporated by reference for their disclosure of suitablecompounds that can be converted to the subject thiocarbonyl derivatives.

[0646] U.S. Pat. Nos. 5,225,565; 5,182,403; 5,164,510; 5,247,090;5,231,188; 5,565,571; 5,547,950; and 5,523,403.

[0647] PCT Application and publications PCT/US93/04850, WO94/01110;PCT/US94/08904, WO95/07271; PCT/US95/02972, WO95/25106; PCT/US95/10992,WO96/13502; PCT/US96/05202, WO96/35691; PCT/US96/12766; PCT/US96/13726;PCT/US96/14135; PCT/US96/17120; PCT/US96/19149; PCT/US97/01970;PCT/US95/12751, WO96/15130; and PCT/US96/00718, WO96/23788.

[0648] Chemical conversion techniques for converting variousintermediates having a CH₂NH₂ on the oxazolidinone ring toCH₂NH—C(S)—CH₃ is disclosed by Hartke, K, Barrmeyer, S., J. prakt. Chem.1996, 338, 251-6. Similarly, conversion of CH₂NHC(═O)CH₃ toCH₂NHC(S)NHCH₃ is reported by Cava, M. P.; Levinson, M. I., ThionationReactions of Lawesson's Reagents, Tetrahedron 1985, 41, 5061-87.

[0649] For the purpose of the present invention, the carbon content ofvarious hydrocarbon containing moieties is indicated by a prefixdesignating the minimum and maximum number of carbon atoms in themoiety, i.e., the prefix C_(i-j) defines the number of carbon atomspresent from the integer “i” to the integer “j”, inclusive. Thus, C₁₋₄alkyl refers to alkyl of 1-4 carbon atoms, inclusive, or methyl, ethyl,propyl, butyl and isomeric forms thereof.

[0650] The terms “C₁₋₂ alkyl”, “C₁₋₃ alkyl”, “C₁₋₄ alkyl”, “C₁₋₅ alkyl”,“C₁₋₆ alkyl”, “C₁₋₈ alkyl”, and “C₁₋₁₆ alkyl” refer to an alkyl grouphaving one to two, one to three, one to four, one to five, one to six,one to eight, or one to sixteen carbon atoms respectively such as, forexample, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl,nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomericforms thereof.

[0651] The terms “C₂₋₄ alkenyl”, “C₂₋₅ alkenyl”, “C₂₋₈ alkenyl”, “C₂₋₁₄alkenyl” and “C₂₋₁₆ alkenyl” refer to at least one double bond alkenylgroup having two to four, two to five, two to eight, two to fourteen, ortwo to sixteen carbon atoms, respectively such as, for example, ethenyl,propenyl, butenyl, pentenyl, pentdienyl, hexenyl, hexdienyl, heptenyl,heptdienyl, octenyl, octdienyl, octatrienyl, nonenyl, nonedienyl,nonatrienyl, undecenyl, undecdienyl, dodecenyl, tridecenyl, tetradecenyland their isomeric forms thereof.

[0652] The terms “C₂₋₅ alkynyl”, “C₂₋₈ alkynyl”, and “C₂₋₁₀ alkynyl”refer to at least one triple bond alkynyl group having two to five, twoto eight, or two to ten carbon atoms respectively such as, for example,ethynyl, propynyl, butynyl, pentynyl, pentdiynyl, hexynyl, hexdiynyl,heptynyl, heptdiynyl, octynyl, octdiynyl, octatriynyl, nonynyl,nonediynyl, nonatriynyl and their isomeric forms thereof.

[0653] The terms “C₃₋₄ cycloalkyl”, “C₃₋₆ cycloalkyl”, “C₅₋₆cycloalkyl”, and “C₃₋₈ cycloalkyl” refer to a cycloalkyl having three tofour, three to six, five to six, or three to eight carbon atomsrespectively such as, for example, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof.

[0654] The terms “C₁₋₄ alkoxy”, “C₁₋₆ alkoxy”, and “C₁₋₈ alkoxy” referto an alkyl group having one to four, one to six, or one to eight carbonatoms respectively attached to an oxygen atom such as, for example,methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, oroctyloxy and their isomeric forms thereof.

[0655] The terms “C₁₋₆ alkylamino”, and “C₁₋₈ alkylamino” refer to analkyl group having one to six, or one to eight carbon atoms respectivelyattached to an amino moiety such as, for example, methylamino,ethylamino, propylamino, butylamino, pentylamino, hexylamino,heptylamino, or octoylamino and their isomeric forms thereof.

[0656] The terms “C₁₋₆ dialkylamino”, and “C₁₋₈ dialkylamino” refer totwo alkyl groups having one to six, or one to eight carbon atomsrespectively attached to an amino moiety such as, for example,dimethylamino, methylethylamino, diethylamino, dipropylamino,methypropylamino, ethylpropylamino, dibutylamino, dipentylamino,dihexylamino, methylhecylamino, diheptylamino, or dioctoylamino andtheir isomeric forms thereof.

[0657] The terms “C₁₋₃ acyl”, “C₁₋₄ acyl”, “C₁₋₅ acyl”, “C₁₋₆ acyl”,“C₁₋₈ acyl”, and “C₂₋₈ acyl” refer to a carbonyl group having an alkylgroup of one to three, one to four, one to five, one to six, one toeight, or two to eight carbon atoms.

[0658] The terms “C₁₋₄ alkoxycarbonyl”, “C₁₋₆ alkoxycarbonyl”, and “C₁₋₈alkoxycarbonyl” refer to an ester group having an alkyl group of one tofour, one to six, or one to eight carbon atoms.

[0659] The term “C₁₋₈ alkyl phenyl” refers to an alkyl group having oneto eight carbon atoms and isomeric forms thereof which is substitutedwith at least one phenyl radical.

[0660] The term “C₂₋₈ alkenyl phenyl” refers to a at least one doublebond alkenyl group having one to eight carbon atoms and isomeric formsthereof which is substituted with at least one phenyl radical.

[0661] The term “C₁₋₈alkyl pyridyl” refers to an alkyl group having oneto eight carbon atoms and isomeric forms thereof which is substitutedwith at least one pyridyl radical.

[0662] The term “C₁₋₈ hydroxyl” refers to an alkyl group having one toeight carbon atoms and isomeric forms thereof attached to a hydroxygroup.

[0663] The term “C₁₋₈ alkylsulfonyl” refers to an alkyl group having oneto eight carbon atoms and isomeric forms thereof attached to a SO₂moiety.

[0664] The term “C₁₋₆ alkylthio” refers to an alkyl group having one tosix carbon atoms and isomeric forms thereof attached to a sulfur atom.

[0665] The term “Het” refers to 5 to 10 membered saturated, unsaturatedor aromatic heterocyclic rings containing one or more oxygen, nitrogen,and sulfur forming such groups as, for example, pyridine, thiophene,furan, pyrazoline, pyrimidine, 2-pyridyl, 3-pyridyl, 4-pyridyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, 3-pyrazinyl, 2-quinolyl, 3-quinolyl, 1-isoquinolyl,3-isoquinolyl, 4-isoquinolyl, 2-quinazolinyl, 4-quinazolinyl,2-quinoxalinyl, 1-phthalazinyl, 4-oxo-2-imidazolyl, 2-imidazolyl,4-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl,4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 4-oxo-2-oxazolyl,5-oxazolyl, 4,5,-dihydrooxazole, 1,2,3-oxathiole, 1,2,3-oxadiazole,1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 2-thiazolyl,4-thiazolyl, 5-thiazolyl, 3-isothiazole, 4-isothiazole, 5-isothiazole,2-indolyl, 3-indolyl, 3-indazolyl, 2-benzoxazolyl, 2-benzothiazolyl,2-benzimidazolyl, 2-benzofuranyl, 3-benzofuranyl, benzoisothiazole,benzisoxazole, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-pyrrolyl,3-pyrrolyl, 3-isopyrrolyl, 4-isopyrrolyl, 5-isopyrrolyl,1,2,3,-oxathiazole-1-oxide, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,5-oxo-1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazol-3-yl,1,2,4-thiadiazol-5-yl, 3-oxo-1,2,4-thiadiazol-5-yl,1,3,4-thiadiazol-5-yl, 2-oxo-1,3,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl,1,2,4-triazol-5-yl, 1,2,3,4-tetrazol-5-yl, 5-oxazolyl, 1-pyrrolyl,1-pyrazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 1-tetrazolyl,1-indolyl, 1-indazolyl, 2-isoindolyl, 7-oxo-2-isoindolyl,1-purinyl,3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, 1,3,4,-oxadiazole,4-oxo-2-thiazolinyl, or 5-methyl-1,3,4-thiadiazol-2-yl, thiazoledione,1,2,3,4-thiatriazole, 1,2,4-dithiazolone. Each of these moieties may besubstituted as appropriate.

[0666] The term halo refers to fluoro, chloro, bromo, or iodo.

[0667] The compounds of the present invention can be converted to theirsalts, where appropriate, according to conventional methods.

[0668] The term “pharmaceutically acceptable salts” refers to acidaddition salts useful for administering the compounds of this inventionand include hydrochloride, hydrobromide, hydroiodide, sulfate,phosphate, acetate, propionate, lactate, mesylate, maleate, malate,succinate, tartrate, citric acid, 2-hydroxyethyl sulfonate, fumarate andthe like. These salts may be in hydrated form.

[0669] When Q is the structure of

[0670] the dotted line in the heterocyclic ring means that this bond canbe either single or double. In the case where the dotted line is adouble bond, the R₃₉ group will not be present.

[0671] The compounds of Formula I of this invention contain a chiralcenter at C5 of the isoxazoline ring, and as such there exist twoenantiomers or a racemic mixture of both. This invention relates to boththe enantiomers, as well as mixtures containing both the isomers. Inaddition, depending on substituents, additional chiral centers and otherisomeric forms may be present in any of A or R₁ group, and thisinvention embraces all possible stereoisomers and geometric forms inthese groups.

[0672] The compounds of this invention are useful for treatment ofmicrobial infections in humans and other warm blooded animals, underboth parenteral and oral administration.

[0673] The pharmaceutical compositions of this invention may be preparedby combining the compounds of this invention with a solid or liquidpharmaceutically acceptable carrier and, optionally, withpharmaceutically acceptable adjuvants and excipients employing standardand conventional techniques. Solid form compositions include powders,tablets, dispersible granules, capsules, cachets and suppositories. Asolid carrier can be at least one substance which may also function as adiluent, flavoring agent, solubilizer, lubricant, suspending agent,binder, tablet disintegrating agent, and encapsulating agent. Inertsolid carriers include magnesium carbonate, magnesium stearate, talc,sugar, lactose, pectin, dextrin, starch, gelatin, cellulosic materials,low melting wax, cocoa butter, and the like. Liquid form compositionsinclude solutions, suspensions and emulsions. For example, there may beprovided solutions of the compounds of this invention dissolved in waterand water-propylene glycol and water-polyethylene glycol systems,optionally containing suitable conventional coloring agents, flavoringagents, stabilizers and thickening agents.

[0674] Preferably, the pharmaceutical composition is provided employingconventional techniques in unit dosage form containing effective orappropriate amounts of the active component, that is, the compoundaccording to this invention.

[0675] The quantity of active component, that is the compound accordingto this invention, in the pharmaceutical composition and unit dosageform thereof may be varied or adjusted widely depending upon theparticular application, the potency of the particular compound, thedesired concentration. Generally, the quantity of active component willrange between 0.5% to 90% by weight of the composition.

[0676] In therapeutic use for treating, or combatting, bacterialinfections in warm-blooded animals, the compounds or pharmaceuticalcompositions thereof will be administered orally, parenterally and/ortopically at a dosage to obtain and maintain a concentration, that is,an amount, or blood-level of active component in the animal undergoingtreatment which will be antibacterially effective. Generally, suchantibacterially effective amount of dosage of active component will bein the range of about 0.1 to about 100, more preferably about 3.0 toabout 50 mg/kg of body weight/day. It is to be understood that thedosages may vary depending upon the requirements of the patient, theseverity of the bacterial infection being treated, and the particularcompound being used. Also, it is to be understood that the initialdosage administered may be increased beyond the above upper level inorder to rapidly achieve the desired blood-level or the initial dosagemay be smaller than the optimum and the daily dosage may beprogressively increased during the course of treatment depending on theparticular situation. If desired, the daily dose may also be dividedinto multiple doses for administration, e.g., 2-4 four times per day.

[0677] When the compounds according to this invention are administeredparenterally, i.e., by injection, for example, by intravenous injectionor by other parenteral routes of administration. Pharmaceuticalcompositions for parenteral administration will generally contain apharmaceutically acceptable amount of the compound or a soluble salt(acid addition salt or base salt) dissolved in a pharmaceuticallyacceptable liquid carrier such as, for example, water-for-injection anda buffer to provide a suitably buffered isotonic solution, for example,having a pH of about 3.5-6. Suitable buffering agents include, forexample, trisodium orthophosphate, sodium bicarbonate, sodium citrate,N-methylglucamine, L(+)-lysine and L(+)-arginine to name but a fewrepresentative buffering agents. The compound of this inventiongenerally will be dissolved in the carrier in an amount sufficient toprovide a pharmaceutically acceptable injectable concentration in therange of about 1 mg/mL to about 400 mg/mL of solution. The resultingliquid pharmaceutical composition will be administered so as to obtainthe above-mentioned antibacterially effective amount of dosage. Thecompounds according to this invention are advantageously administeredorally in solid and liquid dosage forms.

[0678] As a topical treatment an effective amount of Formula I isadmixed in a pharmaceutically acceptable gel or cream vehicle that canbe applied to the patient's skin at the area of treatment. Preparationof such creams and gels is well known in the art and can includepenetration enhancers.

[0679] MIC Test Method

[0680] The in vitro MICs of test compounds were determined by a standardagar dilution method. A stock drug solution of each analog is preparedin the preferred solvent, usually DMSO:H₂O (1:3). Serial 2-folddilutions of each sample are made using 1.0 ml aliquots of steriledistilled water. To each 1.0 ml aliquot of drug is added 9 ml of moltenMueller Hinton agar medium. The drug-supplemented agar is mixed, pouredinto 15×100 mm petri dishes, and allowed to solidify and dry prior toinoculation.

[0681] Vials of each of the test organisms are maintained frozen in thevapor phase of a liquid nitrogen freezer. Test cultures are grownovernight at 35° C. on the medium appropriate for the organism. Coloniesare harvested with a sterile swab, and cell suspensions are prepared inTrypticase Soy broth (TSB) to equal the turbidity of a 0.5 McFarlandstandard. A 1:20 dilution of each suspension is made in TSB. The platescontaining the drug supplemented agar are inoculated with a 0.001 mldrop of the cell suspension using a Steers replicator, yieldingapproximately 10⁴ to 10⁵ cells per spot. The plates are incubatedovernight at 35° C.

[0682] Following incubation the Minimum Inhibitory Concentration (MICμg/ml), the lowest concentration of drug that inhibits visible growth ofthe organism, is read and recorded. The data is shown in Tables I andII. TABLE 1 Oxazolidinone MIC Values (Gram+) SAUR SEPI EFAE SPNE SPYOStructure 9213 12084 9217 9912 152 Comparison*

16 4 8 .5 1 Example 3

4 1 2 .25 .5 Comparison*

2 1 2 .5 1 Example 1

1 .25 .5 .13 .13 Example 5

1 .25 .5 <.125 .25 Example 6

2 1 2 .5 1 Comparison*

.5 .25 1 .13 .25 Example 2

8 2 4 2 4

[0683] TABLE II SAUR SEPI EFAB SPNE SPYO HINF MCAT EFAE Example No. 9213MIC 30593 MIC 12712 MIC 9912 MIC 152 MIC 30063 MIC 30610 MIC 9217 MIC  11 0.25 0.5 <0.125 <0.125 8 1 0.5  2 8 4 8 2 4 >16 >16 4  3 4 1 1 0.250.5 16 4 2  5 1 0.5 0.5 <0.125 0.25 4 2 0.5  6 2 2 2 0.5 1 16 8 2  7 0.50.25 0.5 <0.125 0.25 4 1 0.5  8 2 1 0.5 <0.125 0.25 4 2 0.5  9 0.5 0.250.25 <0.125 <0.125 2 0.5 0.25 10 2 1 0.5 <0.125 0.25 2 1 1 11 0.25 0.250.25 <0.125 0.25 2 1 0.25 12 1 0.5 0.25 <0.125 <0.125 1 0.5 0.5 13 1 1 20.5 1 >16 8 2 14 1 0.5 1 0.25 0.5 8 1 1 15 32 16 32 4 8 >64 64 32 16 8 816 2 8 >64 32 16 17 2 2 4 1 2 64 16 4 18 2 1 2 <0.5 1 32 4 2 19 32 16 3216 16 64 32 32 21 4 4 8 2 4 64 16 8 22, 23 0.5 0.5 1 <0.125 0.25 4 2 124 1 0.25 0.5 <0.125 0.25 4 2 0.5 25 0.5 0.25 0.5 <0.125 <0.125 2 2 0.526 1 0.5 1 0.25 0.5 16 2 1 27 0.5 0.5 0.5 <0.125 0.25 4 2 1 28 0.5 0.250.5 0.25 0.25 2 1 0.5 29 0.25 0.25 0.25 <0.125 <0.125 2 0.5 0.25 30 4 10.5 <0.125 0.25 8 2 1 31 2 1 1 <0.125 0.25 4 1 1 32 16 2 2 0.25 0.25 8 24 33 4 2 1 0.25 0.25 4 2 4 34 2 1 2 0.5 1 >16 4 2 35 1 0.5 1 0.25 0.5 162 1

[0684] As shown in Scheme 1, the intermediates II for the compounds ofthis invention are also intermediates disclosed in the oxazolidinonepatents and published applications hereinabove incorporated byreference. The intermediates IV for this invention are final products(Examples) from the oxazolidinone patents and published applicationshereinabove incorporated by reference.

[0685] As shown in Scheme 1, Step 1, and illustrated in Example 5, theisothiocyanates III can be conveniently prepared by allowing the amineintermediates (II) to react with 1,1′-thiocarbonyldi-2(1H)-pyridone insolvents such as methylene chloride at 0 to 25° C. The thioureas (Ia,R′=H, alkyl₁₋₄) can then be prepared as shown in Step 2 by the reactionof III with ammonia or the appropriate primary amines in solvents suchas 1,4-dioxane or tetrahydrofuran at 0-50° C. Alternatively, asillustrated in Example 6 and shown in Step 3, the thioureas can beprepared by allowing II to react with an appropriate isothiocyanate(R′—N═C═S) in solvents such as tetrahydrofuran at 0-50° C. Thioamides(Ib, R″=H, alkyl₁₋₄) are prepared by allowing II to react with anappropriate dithioester (R′″ S—C(═S)—R″, Step 4 as illustrated inExample 4. This reaction is carried out in aqueous-alcoholic solvents at0-50° C. in the presence of an equivalent of an alkali metal hydroxide.This reaction, especially when R′″ is methyl or ethyl, can be catalyzedby an alkali metal fluoride.

[0686] The reaction of II with R′″—S—C(S)—R′″ (R′″=CH₃, C₂H₅) to give Ib(Step 4) can also be carried out in the presence of a tertiary aminebase such as triethylamine in solvents such as THF, dioxane or methylenechloride at 10-50° C. for 3-48 hr.

[0687] When the reaction conditions are tolerated by the substituents onR (see, for example, Examples 1-3) the thioamides (Ib, R″—H, alkyl₁₋₄)can also be conveniently prepared (Step 5) by allowing the appropriateamide intermediates (IV) to react with reagents such as2,4-bis(p-methoxyphenyl)-1,3-dithiadiphosphetane-2,4-disulfide(Lawesson's Reagent) in 1,4-dioxane, benzene, toluene or tetrahydrofuranat 60-110° C.; phosphorus decasulfide and sodium carbonate intetrahydrofuran at 20-50° C. [Brillon, D., Synthetic Communications, 20,3085 (1990)] or phosphorus decasulfide and sodium fluoride in1,2-dimethoxyethane at 20-50° C. [Hartke, K., Gerber, H.-D., J. Prakt.Chem., 338, 763 (1996)].

[0688] Compounds Ic are prepared (Step 6) by allowing II to react firstwith carbon disulfide and a tertiary amine base such as triethylamine insolvent mixtures containing water and methanol, ethanol or isopropanolat 10-50° C. for 5-24 hours. The resulting intermediate is treated withan alkylating agent (R″″ X where X represents bromo, iodo,alkylsulfonyloxy or arylsulfonyloxy) at 0-30° C. to give compounds Ic.In Step 7, compounds Ic are allowed to react with alkali metal alkoxidesuch as sodium methoxide or potassium ethoxide in the correspondingalkanol as solvent. This reaction is conveniently carried out at thereflux temperature of the alkanol for 1-24 hr.

[0689] In order to more fully illustrate the nature of the invention andthe manner of practicing the same, the following experimental examplesare presented.

EXAMPLE 1(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(I)

[0690]

[0691] A stirred mixture of II (PCT/US94/08904, 3.37 g, 10.0 mmol) indry dioxane (100 mL), under nitrogen was treated with Lawesson's Reagent(4.04 g, 10.0 mml), warmed to reflux during 1 h and refluxed for 1.5 h.The reaction was complete by TLC on silica gel with 10% MeOH—CHCl₃. Itwas kept at ambient temperature for 18 h and concentrated in vacuo.Chromatography of the residue on silica gel with mixtures ofacetone-methylene chloride containing 10-15% acetone gave the productwhich was crystallized from acetone-hexane to give 1: mp 157.5-158.5°C.; HRMS theory for C₁₆H₂₀FN₃O₃S (M⁺): 353.1209; found: 353.1212. Anal.calcd for C₁₆H₂₀FN₃O₃S: C, 54.38; H, 5.38; N, 11.89; S, 9.07. Found: C,54.21; H, 5.58; N, 11.78; S, 8.93.

EXAMPLE 2(S)-N-[[3-[3-Fluoro-4-[4-(5-methyl-1,3,4-thiadiazol-2-yl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(2)

[0692]

[0693] According to Example 1, for the preparation of 1, 21(PCT/US97/01970) was allowed to react with Lawesson's Reagent inrefluxing dioxane to give 2: mp 222-223° C.; HRMS theory forC₁₉H₂₄FN₆O₂S₂ (M+H⁺): 451.1386; found 451.1381.

EXAMPLE 3(S)-N-[[3-[3-Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(3)

[0694] Step A:(S)-N-[[3-[3Fluoro-4-[2′,5′-dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide(32)

[0695] A stirred suspension of 31 (WO95/25106, 0.349 g, 1.00 mmol) in1:1 EtOH:H₂O (5 mL), under nitrogen, was treated with potassium cyanide(0.130 g, 2.00 mmol) and ammonium carbonate (0.701 g, 7.30 mmol), warmedat 65-60° C. for 5 h 15 min and kept at ambient temperature for 17 h 15min. It was then chromatographed on silica gel with mixtures ofMeOH—NH₄OH—CHCl₃ containing 5-20% MeOH and 0.5% NH₄OH to give 0.280 g of32: HRMS calcd for C₁₉H₂₂FN₅O₅: 419.1605 (M⁺); found 419.1613; Anal.calcd for C₁₉H₂₂FN₅O₅.1 H₂O: C, 52.17; H. 5.53; N. 16.01. Found: C,52.44; H, 5.30; N, 16.11.

[0696] Step B:(S)-N-[[3-[3-Fluoro-[2′,5′-doxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(3)

[0697] A stirred suspension of 32 (0.210 g, 0.500 mmol) in dioxane (5.0mL), under nitrogen was treated with Lawesson's Reagent (0.202 g, 0.500mmol), refluxed for 4 h and concentrated in vacuo. The residue waschromatographed on silica gel with mixtures of MeOH—NH₄OH—CHCl₃containing 1-10% MeOH and 0.1-0.5% NH₄OH and the resulting product wascrystallized from MeOH—CHCl₃EtOAc to give 0.0491 g of 3: mp 218.5° C.;HR FAB MS theory for C₁₉H₂₂FN₅O₄S (M⁺): 435.1376; found 435.1370. Anal.calcd for C₁₉H₂₂FN₅O₄S.0.5 H₂O: C, 51.34; H, 5.21; N, 15.76. Found: C,51.69; H, 5.00; N, 15.25.

EXAMPLE 4(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(4)

[0698]

[0699] A solution of 41 (148 mg, 0.500 mmol) and 0.97 M KOH (0.515 mL)in absolute EtOH (5 mL) was added to a solution of ethyl dithioacetate(57 μL, 0.50 mmol) and sodium fluoride (20 mg, 0.47 mmol) in absoluteEtOH (5 mL) and the mixture was kept at ambient temperature for 3 h 40min. Additional ethyl dithioacetate (5 μL) was added after 1 h 55 minand additional 0.97 M KOH (40 mL) and sodium fluoride (6 mg) were addedto the mixture after 3h 5 min. The reaction was followed by TLC onsilica gel with 10% MeOH—CHCl₃ and 30% acetone-CH₂Cl₂. The major producthad an R_(f) on TLC that was the same as that of 4.

EXAMPLE 5(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea(5)

[0700]

[0701] A solution of 51 (PCT/US94/08904, 2.07 g, 7.00 mmol) in CH₂Cl₂was added, dropwise during 30 min, under nitrogen to an ice cold,stirred solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (1.95 g, 8.40mmol) in CH₂Cl₂ (70 mL). The mixture was warmed slowly to ambienttemperature and kept for 18 h. It was then diluted with CH₂Cl₂, washedwith water and aqueous NaCl, dried (Na₂SO₄) and concentrated.Chromatography of the residue on silica gel with 10% acetonitrile-CH₂Cl₂gave 1.60 g of the isothiocyanate: HRMS theory for C₁₅H₁₆FN₃O₃S (M⁺):337.0896; found 337.0888.

[0702] Anhydrous ammonia was bubbled for 7 min through a stirredsolution of the product from Step I (1.00 g, 2.96 mmol) in THF (10 mL)and the mixture was kept at ambient temperature for 3 h 25 min andconcentrated in vacuo. Crystallization of the residue fromacetone-hexane gave 0.861 g of 5: mp 199-199.5° C.; MS m/z 354 (M⁺).Anal. calcd for C₁₅H₁₉FN₄O₃S: C, 50.84; H, 5.40; N, 15.81. Found: C,50.87; H, 5.39; N, 15.72.

EXAMPLE 6(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea(6)

[0703]

[0704] A stirred solution of methyl isothiocyanate (93 mg, 1.27 mmol) inTHF, was treated with 61 (295 mg, 1.00 mmol), kept at ambienttemperature for 18 h and concentrated in vacuo. The residue wasrecrystallized from EtOAc-hexane to give 246 mg of 6: mp 158-160° C.; MSm/z 368 (M⁺). Anal. calcd for C₁₆H₂₁FN₄O₃S: C, 52.16; H, 5.74; N, 15.21.Found: C, 52.20; H, 5.85; N, 15.17.

EXAMPLE 7(S)-cis-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

[0705]

[0706] Step 1: A mixture of(S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideS-oxide (4.50 g, can be obtained according to the procedures disclosedin International Publication No. WO 97/09328) and platinum oxide (697mg) in methanol (164 mL) is shaken on the Parr apparatus under ahydrogen atmosphere at 40 psi for 18 hours. The catalyst is then removedby filtration through Celite, and the filtrate is concentrated underreduced pressure and the residue chromatographed on silica gel (230-400mesh, 350 g), eluting with a gradient of methanol/methylene chloride(3/97-7/93). Pooling and concentration of those fractions with anR_(f)=0.44 by TLC (methanol/chloroform, 10/90) gives(S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide,mp 203-204° C.

[0707] Step 2: A mixture of the compound prepared in Step 1 (2.50 g) andhydroxylamine hydrochloride (2.36 g) in pyridine (30.6 mL) and ethanol(3.4 mL) is stirred in a screw-cap vial at 100° C. for 22 hrs and atambient temperature for 16 hrs, during which additional hydroxylaminehydrochloride (944 mg) and pyridine (4 mL) is added. The reactionmixture is then concentrated under reduced pressure, diluted withsaturated aqueous sodium bicarbonate (100 mL) and saline (50 mL),adjusted to pH 11 with solid sodium carbonate and extracted withmethanol/methylene chloride (10/90, 5×100 mL). The combined organicphase is concentrated under reduced pressure, and the crude product ischromatographed on silica gel (230-400 mesh, 150 g), eluting with agradient of methanol/methylene chloride (6/94-10/90). Pooling andconcentration of those fractions with an R_(f)=0.14 by TLC(methanol/chloroform, 10/90) gives(S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,mp 159-161° C.

[0708] Step 3: A solution of ethyl dithioacetate (105 mL, 0.919 mmol)and sodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under anitrogen atmosphere was treated with a mixture of(S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Step 2,(300 mg, 0.919 mmol) and aqueous potassiumhydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution wasstirred at ambient temperature for 4 hours and was then diluted withmethylene chloride (150 mL) and washed with water (50 mL), aqueouspotassium hydrogen sulfate (1M, 50 mL) and brine (25 mL). The organicphase was dried over anhydrous sodium sulfate and concentrated in vacuo,and the crude product was triturated with methylene chloride/diethylether and filtered to give the title compound, mp 176-177° C. (dec.).

EXAMPLE 8(S)-cis-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0709]

[0710] Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (235 mg,1.01 mmol) in anhydrous methylene chloride (10 mL) at 0° C. under anitrogen atmosphere was treated with a solution of(S-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Example 7, Step 2, (275 mg, 0.843 mmol) in anhydrousmethylene chloride (34 mL) over 30 minutes. The resulting mixture wasstirred at 0° C. for 30 minutes and at ambient temperature for 1 hourand was then diluted with methylene chloride (40 mL), washed with water(25 mL) and brine (25 mL), dried over anhydrous sodium sulfate andconcentrated in vacuo. The crude product was chromatographed on silicagel (70-230 mesh, 20 g), eluting with acetonitrile/methylene chloride(40/60), and those fractions with an R_(f)=0.07 by TLC(acetonitrile/methylene chloride, 30/70) were pooled and concentrated togive(S)-cis-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone,mp 187-190° C. (dec.).

[0711] Step 2: A solution of(S)-cis-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone(Step 1, 290 mg, 0.787 mmol) in anhydrous tetrahydrofuran (39 mL) at 0°C. under a nitrogen atmosphere was treated (bubbled) with a stream ofammonia gas for 5 minutes. The reaction pot was sealed, and theresulting mixture was stirred at 0° C. for 1 hour. The excess ammoniawas then removed under a stream of nitrogen, and the reaction mixturewas concentrated in vacuo to give the crude product. Recrystallizationfrom methanol/methylene chloride/diethyl ether gave the title compound,mp 206-208° C. (dec.).

EXAMPLE 9(S)-trans-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

[0712]

[0713] Step 1:(S)-(−)-N-[[3-[3-fluoro-4-(3,6-dihydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5oxazolidinyl]methyl]acetamide S-oxide (disclosed in InternationalPublication No. WO 97/09328) may be reduced to the corresponding cis andtrans-sulfoxides by catalytic hydrogenation in the presence of acatalyst and solvent. Alternatively, the sulfide by product of thisreduction reaction can be oxidized with an oxidizing agent such NaIO₄ ormeta-chloroperoxybenzoic acid in solvent to provide the cis andtrans-sulfoxides. Alternatively, the sulfide byproduct acn be oxidizedselectively to the trans isomer using t-butyl hydroperoxide and acatalyst such as Ti(OiPr)4 and D-diisopropyl tartrate in a suitablesolvent. The isomeric mixture can then be separated by chromatography toisolate the trans-sulfoxide, mp 211-212° C. (dec.). A mixture of thetrans-sulfoxide,(S)-trans-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide,(0.90 g) and hydroxylamine hydrochloride (0.85 g) in pyridine (11.0 mL)and ethanol (1.2 mL) is stirred in a screw-cap vial at 100° C. for 23hrs and at ambient temperature for 19 hrs, during which additionalhydroxylamine hydrochloride (340 mg) and pyridine (1 mL) is added. Thereaction mixture is then concentrated under reduced pressure, dilutedwith saturated aqueous sodium carbonate (50 mL) and saline (50 mL) andextracted with methanol/methylene chloride (10/90, 6×100 mL). Thecombined organic phase is concentrated under reduced pressure, and thecrude product is chromatographed on silica gel (230-400 mesh, 45 g),eluting with a gradient of methanol/methylene chloride (7.5/92.5-10/90).Pooling and concentration of those fractions with an R_(f)=0.14 by TLC(methanol/chloroform, 10/90) gives(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,mp 138-140° C.

[0714] Step 2: A solution of ethyl dithioacetate (105 mL, 0.919 mmol)and sodium fluoride (39 mg, 0.919 mmol) in ethanol (9.2 mL) under anitrogen atmosphere was treated with a mixture of(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepare in Step 1, (300 mg, 0.919 mmol) and aqueous potassiumhydroxide (1M, 0.92 mL) in ethanol (46 mL). The resulting solution wasstirred at ambient temperature for 17 hours and was then diluted withmethylene chloride (150 mL), washed with water (2×50 mL) and brine (25mL), dried over anhydrous sodium sulfate and concentrated in vacuo. Thecrude product was chromatographed on silica gel (230-400 mesh, 35 g),eluting with methanol/methylene chloride (3/97), and those fractionswith an R_(f)=0.56 by TLC (methanol/chloroform, 10/90) were pooled andconcentrated and the residue recrystallized from methylenechloride/diethyl ether to give the title compound, mp 193-194° C.(dec.).

EXAMPLE 10(S)-trans-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0715]

[0716] Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (192 mg,0.827 mmol) in anhydrous methylene chloride (8.3 mL) at 0° C. under anitrogen atmosphere was treated with a solution of(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Example 9, Step 1, (225 mg, 0.689 mmol) in anhydrousmethylene chloride (28 mL) over 30 minutes. The resulting mixture wasstirred at 0° C. for 30 minutes and at ambient temperature for 40minutes and was then diluted with methylene chloride (20 mL), washedwith water (15 mL) and brine (15 mL), dried over anhydrous sodiumsulfate and concentrated in vacuo. The crude product was chromatographedon silica gel (32-63 mm, 40 g), eluting with a gradient ofacetonitrile/methylene chloride (30/70-60/40) under 15 psi N₂, and thosefractions with an R_(f)=0.12 by TLC (acetonitrile/methylene chloride,30/70) were pooled and concentrated to give(S)-trans-3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone,mp 165-167° C.

[0717] Step 2: A solution of(S)-trans-3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone(Step 1, 230 mg, 0.624 mmol) in anhydrous tetrahydrofuran (31.2 mL) at0° C. under a nitrogen atmosphere was treated (bubbled) with a stream ofammonia gas for 5 minutes. The reaction pot was sealed, and theresulting mixture was stirred at 0° C. for 1 hour. The excess ammoniawas then removed under a stream of nitrogen, and the reaction mixturewas concentrated in vacuo to give the crude product. Trituration withmethanol/methylene chloride/diethyl ether gave the title compound, mp209-210° C. (dec.).

EXAMPLE 11(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide

[0718]

[0719] Step 1: Starting with(S)-cis-(−)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideas prepared in Example 7, Step 1, and following the general procedure ofStep 2, and making non critical variations by substituting(S)-(−)-N-[[3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideS,S-dioxide (disclosed in International Publication No. WO 97/09328) for(S)-cis-(−)-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide,the product(S)-(−)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinoneis obtained, mp 194° C. (dec.).

[0720] Step 2: A solution of ethyl dithioacetate (100 mL, 0.876 mmol)and sodium fluoride (37 mg, 0.876 mmol) in ethanol (8.8 mL) under anitrogen atmosphere was treated with a mixture of(S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Step 1, (300 mg, 0.876 mmol) and aqueous potassiumhydroxide (1M, 0.88 mL) in ethanol (43.8 mL). The resulting mixture wasstirred at ambient temperature for 26 hours, during which additionalethyl dithioacetate (50 mL, 0.438 mmol), sodium fluoride (19 mg, 0.438mmol), aqueous potassium hydroxide (1M, 0.44 mL) and ethanol (3.0 mL)was added, and was then diluted with methylene chloride (150 mL), washedwith water (50 mL), aqueous potassium hydrogen sulfate (1M, 50 mL) andbrine (25 mL), dried over anhydrous sodium sulfate and concentrated invacuo. The crude product was recrystallized from methylenechloride/diethyl ether to give the title compound, mp 186-187° C.(dec.).

EXAMPLE 12(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0721]

[0722] Step 1: A solution of 1,1′-thiocarbonyldi-2(1H)-pyridone (304 mg,1.31 mmol) in anhydrous methylene chloride (13 mL) at 0° C. under anitrogen atmosphere was treated with a solution of(S)-(−)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone,as prepared in Example 11, Step 1, (375 mg, 1.09 mmol) in anhydrousmethylene chloride (88 mL) over 30 minutes. The resulting mixture wasstirred at 0° C. for 30 minutes and at ambient temperature for 30minutes and was then diluted with methylene chloride (40 mL), washedwith water (25 mL) and brine (25 mL), dried over anhydrous sodiumsulfate and concentrated in vacuo. The crude product was chromatographedon silica gel (230-400 mesh, 45 g), eluting with acetonitrile/methylenechloride (7.5/92.5), and those fractions with an R_(f)=0.64 by TLC(acetonitrile/methylene chloride, 20/80) were pooled and concentrated togive(S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone,mp 158-162° C. (dec.).

[0723] Step 2: A solution of(S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-isothiocyanatomethyl-2-oxazolidinone(Step 1, 380 mg, 0.988 mmol) in anhydrous tetrahydrofuran (49 mL) at 0°C. under a nitrogen atmosphere was treated (bubbled) with a stream ofammonia gas for 5 minutes. The reaction pot was sealed, and theresulting mixture was stirred at 0° C. for 1 hour. The excess ammoniawas then removed under a stream of nitrogen, and the reaction mixturewas concentrated in vacuo to give the crude product. Recrystallizationfrom methanol/methylene chloride/diethyl ether gave the title compound,mp 196-198° C. (dec.).

EXAMPLE 13(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioformamide(7)

[0724]

[0725] A stirred mixture of acetic anhydride (0.23 mL, 0.0024 mol) and95-97% formic acid (0.10 mL, 0.0027 mL) was warmed, under nitrogen at50-55° C. for 2 h, cooled to ambient temperature and treated,portionwise during 2 min, with 39 ⁸ (0.45 g, 0.0015 mol). The suspensionwas kept at ambient temperature for 4 h and the resulting solution wastreated with Et₂O (1 mL) and kept at ambient temperature for 18 h. Themixture was diluted with additional Et₂O (10 mL) and the solid wascollected by filtration, washed with Et₂O and dried to give 0.38 g of 6⁹: MS (ES) m/z 324 (M+H⁺), 346 (M+Na⁺); ¹H NMR (300 mHz, CDCl₃) d 3.08(m, 4H), 3.72 (m, 2H), 3.77 (d,d, 1H), 3.89 (m, 4H), 4.04 (t, 1H), 4.80(m, 1H), 6.33 (s, 1H), 7.05 (m, 2H), 7.45 (d,d, 1H), 8.27 (s, 1H).

[0726] A stirred mixture of 6 (0.38 g, 0.00118 mol) in dioxane (20 mL),under nitrogen was treated with 4 (0.51 g, 0.00126 mol), warmed toreflux during 30 min and kept at this temperature for 90 min. It wasthen evaporated under a stream of nitrogen. The residue waschromatographed on silica gel with 1.25% MeOH—CH₂Cl₂ and the slightlyimpure product was rechromatographed on silica gel with 25%EtOAc-CH₂Cl₂. The resulting product was crystallized from EtOAc-methyltert-butyl ether to give 0.114 g of 7: mp 150-155° C. (dec); IR (DRIFT)3322, 1752 cm⁻¹; MS(ES) m/z 340 (M+H⁺), 362 (M+Na⁺); ¹HNMR [300 MHz,(CD₃)₂SO] d 2.94 (m, 4H), 3.72 (m, 4H), 3.77 (d,d, 1H), 3.94 (t, 2H),4.12 (t, 1H), 4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d,1H), 9.33 (d, 1H), 10.59 (s, 1H). Anal. calcd for C₁₅H₁₈FN₃O₃S: C,53.08; H, 5.35; N, 12.38. Found: C, 53.02; H, 5.44; N, 12.36.

EXAMPLE 14(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiopropion-amide(9)

[0727]

[0728] An ice cold, stirred solution of 39 (0.395 g, 0.00134 mol) andtriethyl amine (0.186 mL, 0.0027 mol) in CH₂Cl₂ (20 mL), under nitrogenwas treated, dropwise during 2 min, with a solution of propionylchloride (0.128 mL, 0.00147 mol) in CH₂Cl₂ (3 mL). The mixture was keptin the ice bath for 20 min and at ambient temperature for 1 h. It wasthen diluted with CH₂Cl₂, washed with saturated NaHCO₃, water and brine,dried (MgSO₄) and concentrated. The residue (8) was used without furtherpurification in the next reaction.

[0729] A stirred mixture of the product (8) from the previous reactionand dioxane (20 mL), under nitrogen, was treated, portionwise during 1min, with Lawesson's reagent (0.58 g, 0.0014 mol) and refluxed for 2 h;it was then concentrated. The residue was chromatographed on silica gelwith 2% MeOH—CHCl₃ and the product was crystallized from methyltert-butyl ether to give 0.259 g of 9: mp 138-139° C.; MS(ES) m/z 368(M+H⁺), 390 (M+Na⁺); IR (DRIFT) 3284, 3266, 1748, 1744 cm⁻¹; [α]²⁴ _(D)+20° (MeOH); 1H NMR[300 MHz, (CD₃)₂SO] d 1.12 (t, 3H), 2.56 (q, 2H),2.94 (m, 4H), 3.72 (m, 4H), 3.78 (d,d, 1H), 3.90 (t, 2H), 4.11 (t, 1H),4.93 (m, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.47 (d,d, 1H), 10.30 (broads, 1H). Anal. calcd for C₁₇H₂₂FN₃O₃S: C, 55.57; H, 6.03; N, 11.44.Found: C, 55.68; H, 6.21; N, 11.37.

EXAMPLE 15(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-chlorothioacetamide(11)

[0730]

[0731] A stirred solution of 39 (1.54 g, 5.2 mmol) and triethylamine(750 mg, 7.5 mmol) in CH₂Cl₂ (50 mL), under nitrogen, was treated,dropwise, during 15 min with a solution of chloroacetyl chloride (465mL, 5.8 mmol) in CH₂Cl₂ (30 mL) and kept at ambient temperature for 18h. It was then washed with saturated NaHCO₃ and dilute NaCl, dried(Na₂SO₄) and concentrated. The residue was flash chromatographed onsilica gel with 20-30% acetone-CH₂Cl₂ to give 1.49 g of 10 ⁹ which wasused in the next reaction without further purification.

[0732] A stirred mixture of 10 (0.371 g, 1.0 mmol) and Lawesson'sreagent (0.420 mg, 1.04 mmol) in dioxane (10 mL) was refluxed, undernitrogen for 2 h and concentrated under reduced pressure. The residuewas chromatographed on silica gel with 3-10% acetone-CH₂Cl₂ to give0.143 g of 11: MS (CI) m/z 388 (M+H⁺); ¹H NMR (300 MHz, CDCl₃) d 3.07(m, 4H), 3.77 (d,d, 1H), 3.88 (m, 4H), 4.04 (m, 1H), 4.12 (t, 1H), 4.35(m, 1H), 4.61 (s, 2H), 4.98 (m, 1H), 6.96 (t, 1H), 7.08 (d,d, 1H), 7.44(d,d, 1H), 8.69 (s, 1H). Anal. calcd for C₁₆H₁₉ClFN₃O₃S: C, 49.55; H,4.94; N, 10.83. Found: C, 49.38; H, 5.20; N, 10.27.

EXAMPLE 16(S)-N-[[3-[3-Fluoro-4-(4-moropholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α,α-trifluorothioacetamide(13)

[0733]

[0734] An ice cold stirred solution of 39 (0.590 g, 2.0 mmol) andtriethylamine (640 mL, 4.6 mmol) in CH₂Cl₂ (10 mL) was treated withtrifluoroacetic anhydride (325 mL, 2.3 mmol) and kept in the ice bathfor 10 min and then at ambient temperature. The reaction was followed byTLC on silica gel with 30% acetone-CH₂Cl₂. Additional trifluoroaceticanhydride and triethylamine were added after 3 d (64 mL/125 mL), 4 d(100 mL/220 mL) and 6 d (325 mL/1.0 mL). The reaction was complete 1 hafter the last addition; it was mixed with CH₂Cl₂, washed with water anddilute NaCl, dried (Na₂SO₄) and concentrated. The solid residue wasrecrystallized from acetone-heptane to give 0.566 g of 12: mp 161-164°C. (dec); MS(EI) m/z 391 (M⁺). Anal. calcd for C₁₆H₁₇F₄N₃O₄: C, 49.11;H, 4.38; N, 10.74. Found: C, 48.99; H, 4.56; N, 10.73.

[0735] A stirred mixture of 12 (0.391 g, 1.0 mmol) and Lawesson'sreagent (0.422 g, 1.1 mmol) in dioxane (10 mL) was refluxed, undernitrogen for 2 h, cooled slowly to ambient temperature and concentratedin vacuo. The residue was flash chromatographed on silica gel with 5-15%acetone-CH₂Cl₂ and the product was crystallized from acetone-heptane togive 0.249 g of 13: mp 151-152° C.; MS(EI) m/z 407 (M⁺), 363, 209, 151,95; ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (d,d, 1H), 3.87 (m,4H), 3.95 (m, 1H), 4.14 (t, 1H), 4.32 (m, 1H), 5.01 (m, 1H), 6.92 (t,1H), 7.05 (d,d, 1H), 7.38 (d,d, 1H), 9.03 (s, 1H). Anal. calcd forC₁₆H₁₇F₄N₃O₃S: C, 47.17; H, 4.21; N, 10.31. Found: C, 47.09; H, 4.35; N,10.27.

EXAMPLE 17(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide(15)

[0736]

[0737] A stirred, ice cold solution of 39 (0.590 g, 2.0 mmol) andtriethylamine (611 mL, 4.4 mmol) in CH₂Cl₂ (10 mL), under nitrogen, wastreated, dropwise, with a solution of fluoroacetyl chloride (220 mL, 2.2mmol) in CH₂Cl₂ (5 mL), kept in the ice bath for 10 min and at ambienttemperature for 2 h. It was then diluted with CH₂Cl₂, washed with waterand dilute NaCl, dried (Na₂SO₄) and concentrated. The residue waschromatographed on silica gel with 10-30% acetone-CH₂Cl₂ to give 0.180 gof 14: MS(ES) m/z 356 (M+H⁺), 378 (M+Na⁺).

[0738] A solution of 14 (0.180 g, 0.507 mmol) in dioxane, undernitrogen, was treated with Lawesson's reagent (0.206 g, 0.51 mmol),warmed at 90-100° C. for 1 h and concentrated in vacuo. The residue waschromatographed on silica gel with 15% acetone-CH₂Cl₂ to give 0.161 g of15: MS(EI) m/z 371 (M⁺); ¹H NMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.78(d,d, 1H), 3.87 (m, 4H), 4.03 (m, 1H), 4.11 (t, 1H), 4.38 (m, 1H), 4.98(m, 1H), 5.07 (s, 1H), 5.23 (s, 1H), 6.93 (t, 1H), 7.08 (dd, 1H), 7.42(d,d, 1H), 8.42 (s, 1H). Anal. calcd for C₁₆H₁₉F₂N₃O₃S: C, 51.74; H,5.16; N, 11.31. Found: C, 51.79; H, 5.31; N, 11.02.

EXAMPLE 18(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-difluorothioacetamide(17)

[0739]

[0740] A stirred, ice cold mixture of 39 (0.590 g, 2.0 mmol),difluroacetic acid (190 mL, 2.0 mmol), and 1-hydroxybenzotriazole (0.297g, 2.2 mmol) in DMF (5 mL) under nitrogen, was treated with1-(3-diethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.843 g, 4.4mmol) and kept at ambient temperature for 18 h. It was diluted withCH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) andconcentrated. The solid residue was crystallized form EtOAc-heptane togive 0.617 g of 16: mp 149-150° C.; 1H NMR (300 MHz, CDCl₃) d 3.05 (m,4H), 3.66 (m, 2H), 3.85 (m, 5H), 4.08 (t, 1H), 4.80 (m, 1H), 5.93 (t,J=53.9 Hz, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.39 (d,d, 1H); MS(EI) m/z373 (M⁺). Anal. calcd for C₁₆H₁₈F₃N₃O₄: C, 51.48; H, 4.86; N, 11.26.Found: C, 51.59; H, 4.91; N, 11.29.

[0741] A stirred solution of 16 (0.373 g, 1.00 mmol) in dioxane (10 mL),under nitrogen was treated with Lawesson's reagent (0.404 g, 1.00 mmol),warmed at about 95° C. for 1 h and concentrated in vacuo. Chromatographyof the residue on silica gel with 10% acetone-CH₂Cl₂ and cyrstallizationof the product from EtOAc-heptane gave 0.276 g of 17: mp 125-127° C.;MS(EI) m/z 389 (M⁺), 345, 305, 247, 209, 195, 151, 138, 123, 109, 95; ¹HNMR (300 MHz, CDCl₃) d 3.05 (m, 4H), 3.76 (d,d, 1H), 3.86 (m, 4H), 4.01(m, 1H), 4.12 (t, 1H), 4.30 (m, 1H), 4.99 (m, 1H), 6.20 (t, J=55.9 Hz,1H), 6.92 (t, 1H), 7.06 (d,d, 1H), 7.38 (d,d, 1H), 8.78 (broad s, 1H).Anal. calcd for C₁₆H₁₈F₃N₃O₃S: C, 49.35; H, 4.66; N, 10.79. Found: C,49.37; H, 4.71; N, 10.83.

EXAMPLE 19(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-cyanothioacetamide(19)

[0742]

[0743] An ice cold, stirred mixture of 39 (0.646 g, 2.19 mmol),cyanoacetic acid (0.179 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.351g, 2.6 mmol) in DMF (5 mL), under nitrogen, was treated with1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.997 g,5.2 mmol) and kept at ambient temperature for 24 h. It was diluted withCH₂Cl₂, washed with water and dilute NaCl, dried (Na₂SO₄) andconcentrated. The solid residue was crystallized from EtOAc-heptane togive 0.546 g of 18: mp 172-174° C.: IR (DRIFT) 3316, 2256, 1754, 1684cm⁻¹; MS(EI) m/z 362 (M⁺). Anal. calcd for C₁₇H₁₉FN₄O₄: C, 56.35; H,5.28; N, 15.46. Found: C, 56.33; H, 5.30; N, 15.36.

[0744] A stirred solution of 18 (0.453 mg, 1.25 mmol) in dioxane (10mL), under nitrogen, was treated with Lawesson's reagent (0.505 g, 1.25mmol) and warmed at about 100° C. When the reaction was over (TLC with30% acetone-CH₂Cl₂) the mixture was cooled and concentrated in vacuo.Chromatography of the residue on silica gel with 10-20% acetone-CH₂Cl₂and crystallization of the product from EtOAc-heptane gave 0.110 g of19: mp 186-187° C. (dec); MS(ES) m/z 379 (M+H⁺), 401 (M+Na⁺); ¹H NMR(300 MHz, CDCl₃) d 3.05 (m, 4H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.89 (s,2H), 4.09 (t, 1H), 4.14 (m, 2H), 5.01 (m, 1H), 6.92 (t, 1H), 7.05 (d,d,1H), 7.34 (d,d, 1H), 9.15 (s, 1H); IR (DRIFT) 3244, 2260, 1754 cm⁻¹.Anal. calcd for C₁₇H₁₉FN₄O₃S: C, 53.96; H, 5.06; N, 14.81. Found: C,53.88; H, 5.39; N, 14.61.

EXAMPLE 20(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]α,α-dichlorothioacetamide(21)

[0745]

[0746] A stirred, ice cold solution of 39 (0.885 g, 3.00 mmol) andtriethylamine (975 mL, 7 mmol) in CH₂Cl₂ (15 mL), under nitrogen wastreated, dropwise with a solution of dichloroacetic anhydride (555 mL,3.5 mmol) in CH₂Cl₂ (5 mL) and kept in the ice bath for 15 min and atambient temperature for 18 h. It was diluted with CH₂Cl₂, washed withwater, saturated NaHCO₃ and dilute NaCl, dried (Na₂O₄) and concentrated.Chromatography of the residue on silica gel with 10% acetone-CH₂Cl₂ andcrystallization of the product from acetone-heptane gave 0.463 g of 20:mp 197-198° C. (dec); MS(ES) m/z 406 (M+H⁺), 428 (M+Na⁺); ¹H NMR (300MHz, CDCl₃) d 3.05 (m, 4H), 3.75 (m, 3H), 3.86 (m, 4H), 4.07 (t, 1H),4.83 (m, 1H), 5.94 (s, 1H), 6.92 (t, 1H), 7.06 (m, 2H), 7.41 (d,d, 1H).

[0747] A stirred solution of 20 (0.306 g, 0.75 mmol) in dioxane (5 ml),under nitrogen, was treated with Lawesson's reagent (0.202 g, 0.5 mmol),warmed at about 90° C. for 1 hour, cooled and concentrated in vacuo.Chromatography of the residue on silica gel first with 30%acetone-heptane and then with 10% acetone-methylene chloride andcrystallization of rh product form methylene chloride-heptane gave 0.203g with 21: mp 143-144° cd.; HR17S (EI) calculated for C₁₆H₁₈cl₂ F N₃ O₃S(M) 421.0431. Anal. calcd for C₁₆H₁₈cl₂ F N₃ O₃ S, C, 45.51; H, 4.30;N, 9.95. Found: C, 45.47; H, 4.24; H, 9.88.

EXAMPLE 21(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide(23)

[0748]

[0749] A stirred solution of 39 (0.955 g, 3.2 mmol) and triethylamine(650 mL, 4.5 mmol) in CH₂Cl₂ (50 mL), under nitrogen, was treated,dropwise during 15-20 min with a solution of methyl malonyl chloride(475 mL, 4.3 mmol) in CH₂Cl₂ (10 mL) and kept at ambient temperature for3 days. It was then washed with water and dilute NaCl, dried andconcentrated. The residue was flash chromatographed on silica gel with15-30% acetone-CH₂Cl₂ and the product was crystallized formacetone-hexane to give 0.873 g of 22: mp 150-151° C.; ¹H NMR (300 MHz,CDCl₃) d 3.03 (m, 4H), 3.34 (s, 2H), 3.67 (s, 3H), 3.69 (m, 2H), 3.76(d,d, 1H), 3.85 (m, 4H), 4.00 (t, 1H), 4.78 (m, 1H), 6.90 (t, 1H), 7.06(d,d, 1H), 7.41 (d,d, 1H), 7.57 (t, 1H); MS(ES) m/z 396 (M+H⁺), 418(M+Na⁺); HRMS (FAB) calcd for C₁₈H, FN₃O₆ (M+H⁺) 396.1571, found396.1579. Anal. calcd for C₁₈H₂₂FN₃O₆: C, 54.68; H, 5.61; N, 10.63.Found: C, 54.69; H, 5.68; N, 10.58.

[0750] A stirred solution of 22 (0.395 g, 1.0 mmol) in dioxane (10 mL),under nitrogen, was treated with Lawesson's reagent (0.202 g, 0.5 mmol)and kept at ambient temperature for 4 h 10 min and at 80-90° C. for 1.5h. The reaction was followed by TLC on silica gel with 10% MeOH—CHCl₃.At this time a new, less polar product had begun to form. It was kept atambient temperature for 18 h and at 80° C. for 2 h; additionalLaewsson's reagent (40 mg, 0.099 mmol) was added and warming at 80° C.was continued for 2 h; some starting material still remained. Themixture was concentrated and the residue was chromatographed on silicagel with 15% acetone-CH₂Cl₂ to give 0.348 g of 23: ¹H NMR (300 MHz,CDCl₃) d 3.05 (m, 4H), 3.71 (s, 3H), 3.81 (d,d, 1H), 3.86 (m, 4H), 3.88(s, 2H), 4.07 (t, 1H), 4.19 (m, 2H), 4.99 (m, 1H), 6.91 (t, 1H), 7.07(d,d, 1H), 7.42 (d,d, 1H), 9.52 (s, 1H); IR (DRIFT) 3269, 1743 cm⁻¹;MS(EI) m/z 411 (M⁺). Anal. calcd for C₁₈H₂₂FN₃O₅S: C, 52.54; H, 5.39; N,10.21. Found: C, 52.58; H, 5.43; N, 10.14.

EXAMPLE 22(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(25)

[0751]

[0752] A stirred mixture of 24 (0.150 g, 0.470 mmol) and dioxane (12.5mL), under nitrogen, was treated with Lawesson's reagent (0.20 g, 0.50mmol), refluxed for 1.5 h, kept at ambient temperature for 18 h andconcentrated in vacuo. Flash chromatography of the residue on silica gelwith 5% MeOH—CHCl₃ gave the product which was crystallized from MeOH togive 0.100 g (63.4%) of 25: mp 161-163° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d2.43 (s, 3H), 3.87 (m, 3H), 4.22 (t, 1H), 4.99 (m, 1H), 7.51 (d, 1H),7.77 (m, 2H), 8.26 (s, 1H), 8.97 (d, 1H), 10.35 (broad s, 1H); IR (mull)3259, 3226, 3044, 1752 cm⁻¹; MS(ES) m/z 336 (M+H⁺), 358 (M+Na⁺). Anal.calcd for C₁₄H₁₄FN₅O₂S: C, 50.14; H, 4.21; N, 20.88. Found: C, 50.18; H,4.26; N, 20.94.

EXAMPLE 23(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(25)

[0753]

[0754] A stirred mixture of 26 (0.26 g, 0.938 mmol), ethyl dithioacetate(0.12 g, 0.998 mmol), sodium fluoride (0.040 g, 0.953 mmol) and absoluteEtOH (10 mL), under nitrogen, was treated during 5 min with a solutionof 0.97 M KOH (1.03 mL) in EtOH and kept at ambient temperature for 2 h.It was then diluted with CH₂CL₂ (75 mL), washed with water, 1M KHSO₄,water and brine and evaporated. The residue was flash chromatographed onsilica gel with 5% MeOH—CHCl₃ and the product was crystallized from MeOHto give 0.118 g, mp 164-165° C. (dec) and 0.026 g, mp 162-163° C. (dec)of 25.

EXAMPLE 24(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(28)

[0755]

[0756] A stirred, ice cold solution of 52 (8.80 g, 0.0240 mol) in CH₂Cl₂(25 mL) was treated during 20 min with a solution of trifluoroaceticacid (25 mL) in CH₂Cl₂ (10 mL). The mixture was kept in the ice bath for2 h 15 min and concentrated under reduced pressure. A solution of theresidue in CH₂Cl₂ was washed with saturated NaHCO₃ and dilute NaCl,dried (Na₂SO₄) and concentrated. The residue was used in the nextreaction without further purification. A sample of this material (53)had: ¹H NMR (300 MHz, CDCl₃) d 3.00 (t, 2H), 3.54 (t, 2H), 3.85 (broads, 1H), 5.17 (s, 2H), 6.59 (d, 1H), 6.66 (broad s, 1H), 6.91 (d, 1H),7.23 (s, 1H), 7.36 (m, 5H); MS m/z 269 (M+H⁺).

[0757] An ice cold, stirred mixture of 53 (crude product from theprevious reaction), acetone (200 mL), saturated NaHCO₃ (200 mL) andwater (30 mL) was treated, dropwise during 20 min, with a solution ofbenzyloxyacetyl chloride (4.70 mL, 0.030 mol) in acetone (55 mL), warmedslowly to ambient temperature and kept for 18 h. Additionalbenzyloxytacetyl chloride (1.0 mL) in acetone 35 mL) was added dropwiseand the mixture was kept at ambient temperature for an additional 3 hand diluted with EtOAc and water. A solid was collected by filtrationand dried to give 4.00 g of crude product. The EtOAc solution was dried(Na₂SO₄) and concentrated to give 5.36 g of additional crude product.Crystallization of the product from EtOAc gave a total of 6.35 g of 54¹⁴, mp 157-159.5° C. The analytical sample had: mp 158-159.5° C.; ¹H NMR(300 MHz, CDCl₃) δ 3,16 (t,2H), 4.01(t,2H), 4.21 (s, 2H), 4.69 (s, 2H),5.19 (s, 2H), 6.67 (s, 1H), 6.97 (d, 1H), 7.36 (m, 10H), 7.50 (braod s,1H), 8.15 (d, 1H); MS(EI) m/z (relative intensity) 416 (M⁺, 9), 310 (8),202 (10), 133 (8), 92 (8), 91 (99), 79 (7), 77 (9), 65 (12), 51 (6); IR(mull) 2381, 1722, 1659, 1608, 1558 cm⁻¹. Anal. calcd for C₂₅H₂₄N₂O₄: C,72.10; H, 5.81; N, 6.73. Found: C, 72.05; H, 5.86; N, 6.68.

[0758] A stirred suspension of 54 (1.16 g, 2.78 mmol) in THF (42 mL) wascooled, under nitrogen, to 78° C. and treated, dropwise, during 5 minwith 1.6 M n-BuLi in hexane (1.83 mL). It was kept at 78° C. for 50 min,treated, dropwise, during 5 min with a solution of (R)-(−)-glycidylbutyrate (0.500 g, 3.47 mmol) in THF (2 mL), allowed to warm to ambienttemperature during 3 h and kpet for 18 h. It was then diluted withEtOAc, washed with saturated NH₄Cl, water and brine, dried (MgSO₄) andconcentrated. Chromatography of the residue on silica gel with 3%MeOH—0.2% NH₄OH—CHCl₃ gave 0.60 g (56%) of 55¹⁴: ¹H NMR [300 MHz,(CD₃)₂SO] δ 3.14 (t, 2H), 3.59 (m, 2H), 3.79 (d,d, 1H), 4.03 (m, 3H),4.29 (s, 2H), 4.58 (s, 2H), 4.65 (m, 1H), 5.20 (t, 1H), 7.31 (m, 6H),7.55 (s, 1H), 8.03 (d, 1H); MS(ES) m/z 383 (M+H⁺), 405 (M+Na⁺).

[0759] An ice cold, stirred mixture of 55 (0.60 g, 1.57 mmol),triethylamine (2.2 mL), and CH₂Cl₂ (12 mL), under nitrogen, was treatedwith 3-nitrobenzenesulfonyl chloride (0.44 g, 1.99 mmol) and kept in theice bath for 30 min and at ambient temperature for 60 min. It was thendiluted with CH₂Cl₂, washed with water and brine, dried (Na₂SO₄) andconcentrated. Chromatography of the residue on silica gel with 15%CH₃CN—CH₂Cl₂ gave 0.70 g of 56: ¹H NMR (300 MHz, CDCl₃) d 3.19 (t, J=8.3Hz, 2H), 3.88 (d,d, 1H), 4.04 (t, J=8.4 Hz, 2H), 4.14 (t, 1H), 4.23 (s,2H), 4.42 (m, 2H), 4.70 (s, 2H), 4.84 (m, 1H), 6.97 (m, 1H), 7.34 (m,5H), 7.58 (s, 1H), 7.81 (t, 1H), 8.22 (m, 2H), 8.53 (m, 1H), 8.73 (m,1H); MS(ES) m/z 568 (M+H⁺), 590 (M+Na⁺).

[0760] A stirred mixture of 56 (crude product from 0.00314 mol of 55),acetonitride (70 mL), isopropanol (70 mL) and 29% ammonium hydroxide (70mL) was warmed at 40-44° C. for 7h and kept at ambient temperature for18 h. It was concentrated in vacuo to an aqueous residue with wasextracted with CH₂Cl₂. The extract was washed with water and brine,dried (Na₂SO₄) and concentrated. Chromatography of the residue on silicagel with 8% MeOH0.5% NH₄OH—CHCl₃ gave 1.05 g of 57: ¹H NMR [300 MHz,(CD₃)₂SO] d 2.78 (m, 2H), 3.13 (t, 2H), 3.82 (d,d, 1H), 4.01 (m, 3H),4.29 (s, 2H), 4.58 (s, 2H), 4.58 (m, 1H), 7.31 (m, 6H), 7.54 (broad s,1H), 8.03 (d, 1H); MS(ES) m/z 382 (M+H⁺), 404 (M+Na⁺).

[0761] A mixture of 57 (0.46 g, 1.21 mmol), MeOH (150 mL), 1 M HCl (1.2mL) and 5% palladium-on-carbon catalyst (250 mg) was hydrogenated at aninitial pressure of 49 psi for 5 h. Additional 1M HCl (0.5 mL) andcatalyst (100 mg) were added and hydrogenation was continued for 18 h.The catalyst was removed by filtration and the filtrate was concentratedto give 0.34 g of 27: ¹H NMR [300 MHz, (CD₃)₂SO] δ 3.15 (t, 2H), 3.22(broad s, 2H), 3.84 (d,d, 1H), 4.00 (t, 2H), 4.15 (s, 2H), 4.15 (m, 1H),4.92 (m, 1H), 7.24 (q, 1H), 7.50 (d, 1H), 8.03 (d, 1H), 8.37 (broad s,3H); MS(ES) m/z 2.92 (M+H⁺).

[0762] A suspension of 27 (0.10 g, 0.34 mmol) in a mixture of EtOH (15mL) and 0.97 M KOH (0.7 mL) was added, under nitrogen to a stirredmixture of ethyl dithioacetate (0.0412 g, 0.343 mmol) and sodiumfluoride (0.0137 g, 0.326 mmol) in EtOH (5 mL) and the mixture was keptat ambient temperature for 2h 15 min. Additional 0.97 M KOH (0.2 mL),sodium iodide (6 mg) and ethyl dithioacetate (20 mg) were added and themixture was stirred for 2 h, mixed with CH₂Cl₂ (150 mL), washed withwater, 1M KHSO₄ and brine, dried (Na₂SO₄) and concentrated. The residuewas crystallized from acetone to give 0.0404 g of 28: mp 175-176° C.(dec); MS (FAB) m/z 350 (M+H⁺), 349 (M⁺), 331, 316, 205, 73; HR MS (FAB)calcd for C₁₆H₂₀N₃O₄S (M+H⁺) 350.1174, found 350.1183; ¹H NMR [300 MHz,(CD₃)₂SO] d 2.42 (s, 3H), 3.14 (t, 2H), 3.79 (d,d, 1H), 3.89 (t, 2H),4.00 (t, 2H), 4.12 (m, 3H), 4.83 (t, 1H), 4.90 (m, 1H), 7.25 (d, 1H),7.50 (s, 1H), 8.03 (d, 1H), 10.35 (s, 1H); IR (DRIFT) 3255, 3223, 3068,1747, 1639, 1614 cm⁻¹.

[0763] EXAMPLE 25:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(30)

[0764] A mixture of 58 (3.00 g, 7.00 mmol), THF (60 mL), absolute EtOH(100 mL) and 10% palladium-on-carbon catalyst (415 mg) was hydrogenatedat an initial pressure of 58 psi for 2 h 50 min. The catalyst wasremoved by filtration and the filtrate was concentrated in vacuo to give2.67 g of 59 which was used without further purification in the nextreaction: ¹H NMR (300 MHz, CDCl₃) d 2.16 (broad s), 3.02 (m, 8H), 3.73(d,d, J=3.9, 12.6 Hz, 1H), 3.96 (m, 3H), 4.72 (m, 1H), 6.92 (t, J=9.2Hz, 1H), 7.11 (m, 1H), 7.43 (d,d, J=2.6, 14.3 Hz, 1H); MS(ES) m/z 296(M+H⁺).

[0765] A stirred, ice cold mixture of 59 (2.67 g from the previousreaction), acetone (190 mL) and saturated NaHCO₃ (70 mL) was treated,dropwise during 2-3 min with a solution of benzyloxyacetyl chloride(1.34 mL, 8.61 mmol) in acetone (25 mL), kept in the ice bath for 1 hand diluted with EtOAc. The aqueous layer was extracted with EtOAc andthe combined organic solution was washed with dilute NaCl, dried andconcentrated. Chromatography of the residue on silica gel with 30%acetone-CH₂Cl₂ gave 2.64 g of 60: ¹H NMR (300 MHz, CDCl₃) d 2.28 (broads, 1H), 3.00 (m, 4H), 3.66 (m, 2H), 3.77 (m, 3H), 3.96 (m, 3H), 4.22 (s,2H), 4.61 (s, 2H), 4.74 (m, 1H), 6.88 (t, J=9.2 Hz, 1H), 7.12 (m, 1H),7.35 (s, 5H), 7.46 (d,d, J=2.6, 14.2 Hz, 1H); IR (mull) 3406, 1748, 1647cm⁻¹; HRMS(EI) calcd for C₂₃H₂₆FN₃O₅ (M⁺) 443.1856, found 443.1842.

[0766] A stirred, ice cold mixture of 60 (2.64 g, 6.00 mmol) andtriethylamine (1.14 mL, 8.16 mmol) in CH₂Cl₂ (200 mL), under nitrogen,was treated with 3-nitrobenzenesulfonyl chloride (1.78 g, 8.04 mmol),warmed to ambient temperature and kept for 5 h 20 min. Additional3-nitrobenzenesulfonyl chlroide (180 mg) and triethylamine (0.20 mL)were added and the mixture was kept at ambient temperature for 18 h,diluted with CH₂Cl₂ and washed with water and dilute NaCl, dried(Na₂SO₄) and concentrated. Chromatography of the residue on silica gelwith 40-60% acetone-hexane gave 3.36 g of 77: ¹H NMR (300 MHz, CDCl₃) d3.02 (broad s, 4H), 3.66 (broad s, 2H), 3.78 (broad s, 2H), 3.87 (d,d,J=5.9, 9.1 Hz, 1H), 4.09 (t, J=9.2 Hz, 1H), 4.22 (s, 2H), 4.41 (m, 2H),4.61 (s, 2H), 4.84 (m, 1H), 6.88 (t, J=9.1 Hz, 1H), 7.02 (m, 1H), 7.35(m, 6H), 7.82 (t, J=8.0 Hz, 1H), 8.23 (m, 1H), 8.53 (m, 1H), 8.73 (m,1H); MS(ES) m/z 629 (M+H⁺).

[0767] A solution of 77 (3.36 g, 5.34 mmol) in a mixture of acetonitrile(90 mL), isopropanol (90 mL) and concentrated ammonium hydroxide (90 mL)was warmed at 40-45° C., for 18 h, treated with additional ammoniumhydroxide (30 mL), warmed at 40-45° C. for 8 h, treated with additionalammonium hydroxide (25 mL) and warmed at 45° C. for 18 h. It was thenmixed with water and extracted with CH₂Cl₂. The extract was washed withdilute NaCl, dried (Na₂SO₄) and concentrated. Chromatography of theresidue on silica gel with 5% MeOH-0.5% NH₄OH—CHCl₃ gave 2.44 g of 61:¹H NMR (300 MHz, CDCl₃) d 1.50 (broad s), 3.04 (m, 6H), 3.65 (broad s,2H), 3.81 (m, 3H), 3.99 (t, 1H), 4.21 (s, 2H), 4.61 (s, 2H), 4.66 (m,1H), 6.88 (t, 1H), 7.12 (m, 1H), 7.33 (m, 5H), 7.47 (d,d, 1H); MS(ES)m/z 443 (M+H⁺).

[0768] A solution of 61 (1.45 g, 3.3 mmol) and 1.0 N HCl (3.65 mL) in95% EtOH (150 mL) was treated with 5% palladium-on-carbon catalyst (500mg) and hydrogenated at an initial pressure of 54 psi for 20 h 15 min.Additional 1.0 N HCl (0.5 mL) and catalyst (100 mg) were added andhydrogenation was continued for 20 h 30 min at an initial pressure of 60psi. The reaction was compete by TLC; it was neutralized withconcentrated NH₄OH, filtered and concentrated in vacuo to give 1.18 g of29: ¹H NMR [300 MHz, (CD₃)₂SO] d 2.94 (broad s, 4H), 3.19 (m, 2H), 3.48(broad s, 2H), 3.60 (broad s, 2H), 3.84 (m, 1H), 4.14 (m, 3H), 4.66(broad s, 1H), 4.93 (m, 1H), 7.07 (t, 1H), 7.16 (d,d, 1H), 7.48 (d,d,1H), 8.04 (broad s); IR (mull) 3420, 3099, 3040, 3008, 1755, 1641 cm⁻¹;MS(ES) m/z 353 (M+H⁺). Anal. calcd for C₁₆H₂₂ClFN₄O₄: C, 49.42; H, 5.70;Cl, 9.12; N, 14.41. Found: C, 48.16; H, 5.82; Cl, 10.00; N, 14.28.

[0769] A stirred mixture of ethyl dithioacetate (180 mL, 1.56 mmol),sodium fluoride (72 mg, 1.7 mmol), 29 (500 mg, 1.29 mmol) and EtOH (70mL) under nitrogen, was treated with 0.97M KOH (1.46 mL, 1.42 mmol) andthe resulting solution was kept at ambient temperature for 3 h 35 min,diluted with CHCl₃, washed with water and dilute NaCl, dried (Na₂SO₄)and concentrated. Chromatography of the residue on silica gel with 5%MeOH-0.5% NH₄OH—CHCl₃ and crystallization of the resulting product fromabsolute EtOH gave 0.238 mg (44.9%) 30: mp 163-165° C.; ¹H NMR (300 MHz,CDCl₃) d 2.60 (s, 3H), 3.06 (m, 4H), 3.45 (m, 2H), 3.61 (m, 1H), 3.82(m, 3H), 4.07 (m, 2H), 4.25 (m, 3H), 4.97 (m, 1H), 6.91 (t, 1H), 7.07(m, 1H), 7.45 (d,d, 1H), 7.91 (broad s, 1H); MS(FAB) m/z (relativeintensity) 411 (M+H+, 100), 410 (M⁺, 66.5), 266 (3.1); IR 3292, 1733,1653 cm⁻¹. Anal. calcd for C₁₈H₂₃FN₄O₄S: C, 52.67; H, 5.65; N, 13.65.Found: C, 52.76; H, 5.58; N, 13.64.

EXAMPLE 26(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(32)

[0770]

[0771] An ice cold, stirred mixture of 31 (0.38 g, 0.0012 mol) andtriethylamine (0.38 mL, 0.0027 mol) in THF (12 mL), under nitrogen, wastreated with ethyl dithioacetate (0.16 mL, 0.0014 mol) and then kept atambient temperature for 24.5 h and concentrated in vacuo. A solution ofthe residue in CH₂Cl₂ was washed with saturated NaHCO₃, water and brine,dried (MgSO₄) and concentrated. Crystallization of the residue fromEtOAc-hexane gave 0.355 g of 32: mp 155-156° C.; MS(ES) m/z 370 (M+H⁺),392 (M+Na⁺); IR (DRIFT) 3206, 3042, 1759, 1738 cm⁻¹; ¹H NMR (300 MHz,CDCl₃) d 2.60 (s, 3H), 2.95 (s, 4H), 3.43 (m, 4H), 3.82 (d, d, 1H), 4.08(m, 2H), 4.27 (m, 1H), 4.98 (m, 1H), 7.06 (m, 1H), 7.33 (broad s, 1H),7.51 (d, 1H), 8.03 (broad s, 1H). Anal. calcd for C₁₆H₂₀FN₃O₂S₂: C,52.01; H, 5.46; N, 11.37. Found: C, 51.86; H, 5.43; N, 11.20.

EXAMPLE 27(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide,thiomorpholine S-oxide (34)

[0772]

[0773] An ice cold, stirred mixture of sodium metaperiodate (1.08 g,5.05 mmol) and water (12 mL), under nitrogen, was treated with 62 (1.5g, 4.8 mmol) and MeOH (17 mL) and kept at 6° C. for 18 h and at 4° C.for 3 h. It was then treated with additional sodium metaperiodate (0.1g), kept at 4° C. for 3 h and extracted with CHCl₃. The extract wasdried (MgSO₄) and concntrated to give 1.4 g of 63: ¹H NMR [300 MHz,(CD₃)₂SO] d 2.84 (m, 2H), 3.01 (m, 2H), 3.16 (m, 2H), 3.50 (m, 3H), 3.65(m, 1H), 3.77 (d,d, 1H), 4.03 (t, 1H), 4.66 (m, 1H), 5.18 (t, 1H), 7.16(m, 2H), 7.52 (m, 1H); MS(ES) m/z 329 (M+H⁺), 351 (M+Na⁺).

[0774] An ice cold, stirred mixture of 63 (1.27 g, 3.87 mmol) andtriethylamine (0.732 mL, 5.25 mmol) in CH₂Cl₂ (130 mL), under nitrogen,was treated with m nitrobenzenesulfonyl chloride (1.15 g, 5.19 mmol) andkept at ambient temperature for about 24 h. It was diluted with CH₂Cl₂,washed with water and brine, dried (Na₂SO₄) and concentrated to give 78which was used in the next reaction without purification.

[0775] A stirred mixture of the product (78) from the previous reaction,acetonitrile (70 mL) and isopropanol (70 mL) was treated withconcentrated ammonium hydroxide (70 mL, 29.9% NH₃) and kept at 40° C.for 2 h, at ambient temperature for 18 h and at 40-45° C. for 4 h; itwas concentrated to about 50 mL, diluted with water and extracted withCH₂Cl₂. The extracts were washed with water and brine, dried (MgSO₄) andconcentrated. Chromatography of the residue on silica gel with 5%MeOH—CHCl₃ gave 0.58 g of 33: MS(ES) m/z 328 (M+H⁺), 350 (M+Na); ¹H NMR[300 MHz, (CD₃)₂SO] d 2.81 (m, 4H), 3.01 (m, 2H), 3.16 (m, 2H), 3.30(broad s), 3.49 (m, 2H), 3.80 (d,d, 1H), 4.01 (t, 1H), 4.58 (m, 1H),7.19 (m, 2H), 7.51 (m, 1H).

[0776] A stirred suspension of 33 (3.7 g, 0.011 mol) and triethylamine(3.5 mL, 0.025 mol) in THF (120 mL) was cooled, in an ice bath, undernitrogen, treated, dropwise during 2 min, with a solution of ethyldithioacetate (1.47 mL, 0.0128 mol) in THF (2 mL) and kept at ambienttemperature for 22 h. The resulting solution was concentrated and theresidue crystallized from acetonitrile to give 3.61 g of 34: mp 176-177°C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 2.85 (m, 2H), 3.01 (m,2H), 3.18 (m, 3H), 3.50 (m, 2H), 3.78 (d,d, 1H), 3.89 (broad s, 2H),4.12 (t, 1H), 4.92 (m, 1H), 7.18 (m, 2H), 7.49 (m, 1H), 10.33 (s, 1H);IR (DRIFT) 3186, 3102, 1741 cm⁻¹; MS(ES) m/z 386 (M+H⁺), 408 (M+Na⁺).Anal. calcd for C₁₆H₂₀FN₃O₃S₂∘0.05 H₂O: C, 48.71; H, 5.37; N, 10.65; S,16.26; H₂O, 2.38. Found: C, 48.75; H, 5.17; N, 10.72; S, 16.07; H₂O,1.72.

EXAMPLE 28(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiomorpholine S, S-dioxide (36)

[0777]

[0778] A stirred mixture of 62 (0.399 g, 0.00128 mol) in 25%water/acetone (12 mL), under nitrogen was treated withN-methylmorpholine, N-oxide (0.45 g, 0.00384 mol) and 0.1 mL of a 2.5 wt% solution of osmium tetroxide in tert-butanol. It was kept at ambienttemperature for 18 h, mixed with saturated NaHSO₃ (50 mL) and extractedwith CH₂Cl₂. The extract was washed with saturated NaHSO₃ and brine,dried (Na₂SO₄) and concentrated. The residue was mixed with 3.5%MeOH—CH₂Cl₂ and filtered; the solid was dissolved in 15% MeOH—CH₂Cl₂ andconcentrated to give 0.29 g of 64. The filtrate was chromatographed onsilica gel with 3.5% MeOH—CH₂Cl₂ to give 0.1 of additional 64: MS(ES)m/z 345 (M+H⁺), 367 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 3.26 (m, 4H),3.44 (m, 4H), 3.60 (m, 2H), 3.80 (d,d, 1H), 4.05 (t, 1H), 4.69 (m, 1H),7.22 (m, 2H), 7.54 (d, 1H).

[0779] A stirred mixture of 64 (0.39 g, 0.00113 mol) and triethylamine(0.214 mL, 0.00154 mol) in CH₂Cl₂ (37 mL) was cooled, under nitrogen, inan ice bath and treated, portionwise during 5 min, with3-nitrobenzenesulfonyl chloride (0.335 g, 0.00151 mol). The mixture waskept in the ice bath for 20 min and at ambient temperature for 18 h andconcentrated in vacuo. A stirred solution of the residue in 2-propanol(25 mL) and acetonitrile (25 mL), under nitrogen, was treated with 30%NH₄OH (25 mL), warmed at 50-55° C. for 6 h and kept at ambienttemperature for 48 h. It was concentrated to remove the organicsolvents, diluted with water and extracted with CH₂Cl₂. The extract waswashed with water and brine, dried (MgSO₄) and concentrated. Flashchromatography of the residue on silica gel with 6% MeOH—0.4%NH₄OH—CHCl₃ gave 0.29 g of 35: ¹H NMR [300 MHz, (CD₃)₂SO] d 1.59 (broads, 2H), 2.78 (m, 2H), 3.24 (m, 4H), 3.43 (m, 4H), 3.81 (d,d, 1H), 4.01(t, 1H), 4.57 (m, 1H), 7.18 (m, 2H), 7.52 (m, 1H); MS(ES) m/z 344(M+H⁺), 366 (M+Na⁺).

[0780] A stirred, ice cold suspension of 35 (0.28 g, 0.85 mmol) in amixture of Et₃N (0.26 mL, 1.9 mmmol) and THF (10 mL) was treated withethyl dithioacetate (0.11 mL, about 6 drops) and kept in the ice bathfor 20 min and then at ambient temperature; the reaction was followed byTLC. After 20 h there was still a suspension and only partial reaction;additional THF (10 mL) and ethyl dithioacetate (3 drops) were added.After an additional 48 h the reaction was still incomplete; thesuspension was treated with CH₂Cl₂ (10 mL) and kept for 72 h. At thistime almost complete solution and an almost complete conversion toproduct had been obtained. An additional drop of ethyl dithioacetate wasadded and the mixture was kept at ambient temperature for 5 d andconcentrated in vacuo. The residue was mixed with EtOAc, washed withsaturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated.Crystallization of the residue from MeOH—EtOAc gave 0.209 g of 36: mp197-198° C.; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.42 (s, 3H), 3.24 (m, 4H),3.43 (m, 4H), 3.78 (d,d, 1H), 3.88 (m, 2H), 4.12 (t, 1H), 4.92 (m, 1H),7.18 (m, 2H), 7.50 (m, 1H), 10.37 (broad s, 1H); IR (mull) 3300, 3267,1743 cm⁻¹; MS(ES) m/z 424 (M+Na⁺). Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C,47.87; H, 5.02; N, 10.47. Found: C, 47.84; H, 5.23; N, 10.28.

EXAMPLE 29(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide(38)

[0781]

[0782] A stirred mixture of 65 (1.8 g, 0.00396 mol), pyridine (30 mL)and absolute EtOH (3 mL), under nitrogen, was treated with hydroxylaminehydrochloride (1.44 g, 0.0207 mol), warmed to the reflux temperatureduring 2 h, refluxed for 3.5 h, kept at ambient temperature for 18 h andat reflux for 4 h. It was concentrated in vacuo and the residue wasmixed with water, adjusted to pH 11 with saturated NaHCO₃ and extractedwith Et₂O. The extracts were washed with brine, dried (Na₂SO₄) andconcentrated. Chromatography of the residue on silica gel with 5%MeOH—0.35% NH₄OH—CHCl₃ gave 0.75 g of recovered 65 and 0.72 g of 66: ¹HNMR [300 MHz, (CD₃)₂SO] d 1.40 (s, 9H), 1.72 (broad s, 2H), 2.78 (m,2H), 2.97 (m, 4H), 3.40 (m, 4H), 3.80 (d,d, 1H), 4.00 (t, 1H), 4.59 (m,1H), 7.27 (d, 2H); MS(ES) m/z 413 (M+H⁺), 435 (M+Na⁺).

[0783] An ice cold, stirred mixture of 66 (0.75 g, 0.0018 mol) andtriethylamine (0.315 mL, 0.00225 mol) in THF (12 mL), under nitrogen,was treated, dropwise with benzyl chloroformate (0.29 mL, 0.0020 mol),kept in the ice bath for 15 min and at ambient temperature for 2 h andconcentrated in vacuo. The residue was mixed with CH₂Cl₂ and washed withsaturated NaHCO₃, water and brine, dried (Na₂SO₄) and concentrated. Thisresidue was mixed with Et₂O and filtered to give 0.939 g of 67: mp116-118° C.; ¹H NMR (300 MHz, CDCl₃) d 1.48 (s, 9H), 3.08 (m, 4H), 3.53(m, 4H), 3.60 (m, 2H), 3.73 (m, 1H), 3.96 (t, 1H), 4.76 (m, 1H), 5.10(s, 2H), 5.21 (m, 1H), 7.07 (d, 2H), 7.31 (s, 5H); MS(ES) m/z 547(M+H⁺), 569 (M+Na⁺).

[0784] Compound 67 (0.805 g, 0.00147 mol) was added with stirring,portionwise during 5 min, under nitrogen, to ice cold trifluoroaceticacid (9 mL). The resulting solution was kept in the ice bath for 1 h andthen concentrated under a stream of nitrogen. The residue was mixed withice and saturated NaHCO₃ and extracted with CH₂Cl₂; the extract waswashed with water and brine, dried (Na₂SO₄) and concentrated to give0.63 g of product. The combined aqueous layer was reextracted withEtOAc; the extracts were washed with water and brine, dried (Na₂SO₄) andconentrated to give additional product. The combined product amounted to0.68 g of 68 which was used in the next reaction without furtherpurification.

[0785] An ice cold, stirred mixture of 68 (0.68 g, 0.00152 mol),saturated NaHCO₃ (15.2 mL) and acetone (40 mL), under nitrogen wastreated, dropwise during 15 min, with a solution of benzyloxyacetylchloride (0.29 mL, 0.0019 mol) in acetone (5 mL), kept at ambienttemperature for 6 h, diluted with EtOAc and washed with water and brine.The extract was dried (MgSO₄) and concentrated in vacuo to give 0.72 gof 69: MS(ES) m/z 395 (M+H⁺), 617 (M+Na⁺); 1H NMR (300 MHz, CDCl₃) d3.12 (m, 4H), 3.59 (m, 4H), 3.74 (m, 3H), 3.96 (t, 1H), 4.22 (s, 2H),4.62 (s, 2H), 4.75 (broad s, 1H), 5.10 (s, 2H), 5.22 (m, 1H), 7.08 (d,2H), 7.33 (m, 10H).

[0786] A mixture of 69 (0.72 g, 0.0012 mol), MeOH and 5%palladium-on-carbon catalyst (0.4 g) was hydrogenated at an initialpressure of 45 psi for 4 h. By TLC (8% MeOH—0.5% NH₄OH—CHCl₃) thestarting material had been reduced and two products formed. 1MHydrochloric acid (1.34 mL) was added and hydrogenation was continued atan initial pressure of 40 psi for 21 h. By TLC only the more polarproduct remained. The catalyst was removed by filtration and thefiltrate was concentrated to give 0.40 g of 37: MS(ES) m/z 371 (M+H⁺),393 (M+Na⁺); ¹H NMR [300 MHz, (CD₃)₂SO] d 3.02 (s, 4H), 3.20 (m, 2H),3.43 (s, 2H), 3.56 (s, 2H), 3.84 (m, 1H), 3.84 (broad s), 4.10 (s, 2H),4.14 (t, 1H), 4.96 (m, 1H), 7.26 (d, 2H), 8.41 (broad s, 3H).

[0787] A stirred suspension of 37 (0.38 g) in a solution of Et₃N (0.31mL) and THF (10 mL), under nitrogen, was treated with ethyldithioacetate (0.13 mL, about 7 drops) and kept at ambient temperaturefor 7 d; the reaction was followed by TLC (8% MeOH 0.5% NH₄OH—CHCl₃).Additional ethyl dithioacetate (2 drops) was added after 24 h; after 30h CH₂Cl₂ (10 mL) and ethyl dithioacetate (3 drops) were added; after 48h additional triethylamine (0.3 mL) was added. The mixture wasconcentrated in vacuo and the residue was mixed with ice and saturatedNaHCO₃ an extracted with CH₂Cl₂. The extract was washed with water andbrine, dried (MgSO₄) and concentrated. The residue was chromatographedon silica gel with 2.5% MeOH—CH₂Cl₂ and the product was crystallizedfrom MeOH to give 0.182 g of 38: mp 110-111° C. (dec); MS(ES) m/z 429(M+H⁺), 451 (M+Na⁺); HRMS (FAB) calcd for C₁₈H₂₃F₂N₄O₄S (M+H⁺) 429.1408,found 429.1415; IR (DRIFT) 1760, 1652, 1639 cm⁻¹; [α²⁴ _(D) 8° (MeOH).

EXAMPLE 30(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea(44)

[0788]

[0789] A solution of 26 (0.190 g, 0.685 mmol) in CH₂Cl₂ (20 mL) wasadded, dropwise during 20 min, under nitrogen, to an ice cold, stirredsolution of 1,1-thiocarbonyldi-2(1H)-pyridone (0.193 g, 0.831 mmol) inCH₂Cl₂ (7 mL). The mixture was kept in the ice bath for 20 min and atambient temperature for 2 h, diluted with CH₂Cl₂, washed with water andbrine, dried (MgSO₄) and concentrated. Chromatography of the residue onsilica gel with 10-15% CH₃CN—CH₂Cl₂ gave 0.11 g of 79 which was used inthe next reaction without further purification: MS(ES) m/z 320 (M+H⁺),342 (M+Na⁺).

[0790] A stirred, ice cold solution of 79 (0.10 g, 0.31 mmol) in THF (15mL) was treated with excess anhydrous ammonia and kept in the ice bathfor 90 min. It was then evaporated under a stream of nitrogen to avolume of about 5 mL to give a solid which was collected by filtrationand washed with cold THF to give 0.105 g of 44: mp 214-215° C.; ¹H NMR[300 MHz, (CD₃)₂SO] d 3.82 (m, 3H), 4.18 (t, 1H), 4.89 (broad s, 1H),7.20 (broad s, 2H), 7.50 (d, 1H), 7.79 (m, 2H), 7.93 (t, 1H), 8.26 (s,1H), 8.97 (s, 1H); MS(ES) m/z 337 (M+H⁺), 359 (M+Na⁺). Anal. calcd forC₁₃H₁₃FN₆O₂S: C, 46.42; H, 3.90; N, 24.99. Found: C, 46.22; H, 3.98; N,24.55.

EXAMPLE 31(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea(45)

[0791]

[0792] An ice cold, stirred solution of1,1-thiocarbonyl-2(1H)-dipyridone (0.123 g, 0.530 mmol) in CH₂Cl₂ (5mL), under nitrogen, was treated with a suspension of 29 (0.17 g, 0.4mmol) in CH₂Cl₂ (20 mL) and then during 10 min with a solution oftriethylamine (0.111 mL, 0.8 mmol) in CH₂Cl₂ (10 mL). It was kept in theice bath for 30 min, at ambient temperature for 2 h and at <0° C. for 18h. It was then diluted with CH₂Cl₂, washed with water and brine, dried(MgSO₄) and concentrated. The residue (80) was used without furtherpurification in the next reaction. A sample of 80 that was purified byflash chromatography on silica gel with 10-20% acetonitrile-CH₂Cl₂ had:¹H NMR (300 MHz, CDCl₃) d 1.60 (broad s), 3.07 (m, 4H), 3.45 (m, 2H),3.85 (m, 4H), 3.97 (d,d, 1H), 4.16 (t, 1H), 4.21 (s, 2H), 4.82 (m, 1H),6.95 (t, 1H), 7.13 (d,d, 1H), 7.47 (d,d, 1H); MS m/z 395 (M+H⁺); 417(M+Na⁺).

[0793] Excess anhydrous ammonia was bubbled into a stirred, ice coldsolution of 80 (crude product from the previous reaction) in THF (25 mL)and the mixture was kept in the ice bath for 90 min and concentratedunder a stream of nitrogen. The residue was chromatographed on silicagel with 5% MeOH—0.4% NH₄OH—CHCl₃ and the product was crystallized fromacetonitrile to give 0.0544 g of 45: mp 209-210° C.; ¹H NMR [300 MHz,(CD₃)₂SO] d 294 (broad s, 4H), 3.47 (broad s, 2H), 3.60 (broad s, 2H),3.78 (broad s, 3H), 4.07 (t, 1H), 4.10 (d, J=5.5 Hz, 2H), 4.63 (t, J=5.5Hz, 1H), 4.81 (broad s, 1H), 7.05 (t, 1H), 7.16 (d,d, 1H), 7.15 (broads, 2H), 7.49 (d,d, 1H), 7.91 (t, 1H); IR (mull) 3443, 3403, 3321, 3202,3081, 1753, 1655, 1648 cm⁻¹; HRMS (FAB) calcd for C₁₇H₂₃FN₆O₄S (M+H⁺)412.1454, found 412.1447. Anal. calcd for C₁₇H₂₂FN₅O₄S: C, 49.63; H,5.39; N, 17.02. Found: C, 49.63; H, 5.48; N, 16.99.

EXAMPLE 32(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thiourea(46)

[0794]

[0795] An ice cold, stirred solution of1,1-thiocarbonyldi-2(1H)-pyridone (0.096 g, 0.41 mmol) in CH₂Cl₂ (5 mL)was treated with a suspension of 27 (0.10 g, 0.34 mmol) in CH₂Cl₂ (15mL) and then with 0.05 mL (0.36 mmol) of triethylamine. It was kept inthe ice bath for 30 min and at ambient temperature for 2 h, diluted withCH₂Cl₂, washed with water and brine, dried (MgSO₄) and concentrated.Chromatography of the residue on silica gel with 20-40% CH₃CN—CH₂Cl₂gave 0.04 g of 81.

[0796] Excess anhydrous ammonia was bubbled into an ice cold solution of81 (0.04 g) in THF (30 mL) and the mixture was kept in the ice bath for80 min and concentrated under a stream of nitrogen. The residue wascrystallized from CH₃CN to give 0.0151 g of 46: mp 214-215° C. (dec); MS(FAB) m/z 351 (M+H⁺), 350 (M⁺), 319, 304, 147; HRMS (FAB) calcd forC₁₅H₁₉N₄O₄S (M+H⁺) 351.1127, found 351.1130; IR (DRIFT) 3329, 3296,3196, 1746, 1655, 1626 cm⁻¹.

EXAMPLE 33(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiomorpholine S-oxide (47)

[0797]

[0798] A suspension of 33 (0.30 g, 0.92 mmol) in CH₂Cl₂ (7 mL) wasadded, during 20 min, to an ice cold, stirred mixture of1,1-thiocarbonyldi-2(1H)-pyridone (0.258 g, 1.11 mmol) and CH₂Cl₂ (20mL). The mixture was kept in the ice bath for 20 min and at ambienttemperature for 2 h, mixed with CH₂Cl₂ (50 mL), washed with water andbrine, dried (MgSO₄) and concentrated. Chromatography of the product onsilica gel with 20-50% CH₃CN—CH₂Cl₂ gave 0.27 g of 82 which was used inthe next reaction: MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺).

[0799] A stirred, ice cold solution of 82 (0.27 g, 0.73 mmol) in THF (15mL), under nitrogen, was treated with excess anhydrous ammonia, kept inthe ice bath for 1 h and concentrated; crystallization of the residuefrom MeOH gave 0.175 g of 47; mp 212-213° C.; ¹H NMR [300 MHz, (CD₃)₂SO]d 2.83 (m, 2H), 3.01 (m, 2H), 3.17 (m, 2H), 3.50 (t, 2H), 3.78 (broad s,3H), 4.08 (t, 1H), 4.80 (broad s, 1H), 7.17 (m, 2H), 7.17 (broad s, 2H),7.50 (d, 1H), 7.90 (t, 1H); MS(ES) m /z 409 (M+Na⁺); IR (mull) 3335,3284, 3211, 3175, 3097, 1750, 1630 cm⁻¹. Anal. calcd for C₁₅H₁₉FN₄O₃S₂:C, 46.62; H, 4.95; N, 14.50. Found: C, 46.50; H, 4.95; N, 14.40.

EXAMPLE 34(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-S-methyldithiocarbamate(48)

[0800]

[0801] An ice cold, stirred mixture of 39 (0.59 g, 0.0020 mol), EtOH(1.5 mL), water (2 drops) and triethylamine (0.613 mL, 0.00440 mol),under nitrogen, was treated with carbon disulfide (0.066 mL, 0.0011 mol)and kept in the ice bath for 2 h and at ambient temperature for 18 h. (Asolution was obtained after the addition of carbon disulfide; a whiteprecipitate began to form soon after the mixture was warmed to ambienttemperature.) The thick suspension was treated, dropwise during 2 min,with a solution of methyl iodide (0.137 mL, 0.00220 mol) in EtOH (2 mL)and the mixture was kept at ambient temperature for 1.5 h andconcentrated in vacuo. A solution of the residue in EtOAc was washedwith saturated NaHCO₃, water and brine, dried (MgSO₄) and concentrated.The residue was chromatographed on silica gel with 1.8% MeOH—CH₂Cl₂ andthe product was crystallized from EtOAc to give 0.197 g of 48: mp154-155° C.; IR (mull) 3354, 3346, 1726 cm⁻¹. Anal. calcd forC₁₆H₂₀FN₃O₃S₂: C, 49.85; H, 5.23; N, 10.90. Found: C, 49.73; H, 5.25; N,10.82.

EXAMPLE 35(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl-O-methylthiocarbamate(50)

[0802]

[0803] A stirred mixture of 48 (0.200 g, 0.518 mmol), sodium methoxide(0.003 g, 0.06 mmol) and MeOH (5 mL), under nitrogen, was refluxed for 4h and kept at ambient temperature for 18 h. It was found that thestarting material and product had similar mobilities on TLC. thereaction was therefore followed by MS(ES). Starting material was stillpresent. The mixture was refluxed for 3 h, additional sodium methoxide(0.005 g) was added and reflux was continued for 2 h. It was kept atambient temperature for 18 h, refluxed for 1 h, kept at ambienttemperature 1.5 h and concentrated in vacuo. The residue was mixed withice, the pH was adjusted to 9-10 with 1M KHSO₄ and saturated NaHCO₃ andthe mixture was extracted with CH₂Cl₂. The extract was washed with waterand brine, dried (MgSO₄) and concentrated. The residue waschromatographed on silica gel with 5% acetone-CH₂Cl₂ and the product wascrystallized from EtOAc-hexane to give 0.107 g of 50: mp 128-129° C.;MS(ES) m/z 370 (M+H⁺), 392 (M+Na⁺); IR (DRIFT) 3282, 3251, 1753, 1735cm⁻¹; ¹H NMR [300 MHz, (CD₃)₂SO] d 2.94 (m, 4H), 3.47, 374 (m,m, 7H),3.86, 3.91 (s,s, 3H), 4.10 (m, 1H), 4.73, 4.86 (m,m, 1H), 7.05 (t, 1H),7.16 (d,d, 1H), 7.47 (d,d, 1H), 9.41, 9.50 (s,s, 1H). Anal. calcd forC₁₆H₂₀FN₃O₄S: C, 52.02; H, 5.46; N, 11.38. Found: C, 51.97; H, 5.49; N,11.35.

[0804] When in the procedure of Example 35 an appropriate amount ofsodium ethoxide was substituted for sodium methoxide, the compound ofExample 36 below in Table A was obtained.

[0805] When in the procedure of Example 1 an appropriate amount of(S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isopropylcarboxamide,(S)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropylcarboxamide,or(S)-N-[[3-[3,5-difluoro-4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamidewas substituted for(S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide(Compound 11) and the general procedures of Example 1 was followed, thecompounds of Examples 37, 38 and 39 respectively as set forth below inTable A were obtained. The isopropylcarboxamide and thecyclopropylcarboxamide are obtained by following the procedure inExample 5 of U.S. Pat. No. 5,688,792 only substituting isobutyricanhydride and cyclopropane carbonyl chloride respectively for aceticanhydride in step 7. The acetamide is obtained as described in U.S. Pat.No. 5,688,792 at Example 4.

[0806] When in the procedure of Example 5, step B, an excess amount ofdimethylamine in THF is substituted for anhydrous ammonia, the compoundof Example 40 set forth below in Table A is obtained. TABLE A

Example No. Compound R, R′ 36 (S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-O- ethylthiocarbamate; mp 120° C.,MS(ES) m/z 384(M + H⁺). Anal. calcd for C₁₇H₂₂FN₃O₄S: C, 53.25; H, 5.78;N, 10.96. Found: C, 53.23; H, 5.82; N, 10.92. R = H, R′ = OC₂H₅ 37(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide; mp152-153° C. (dec.); Anal. calcd for C₁₈H₂₄FN₃O₃S: C, 56.67; H, 6.34; N,11.02. Found: C, 56.58; H, 6.41; N, 10.81 R = H, R′ = CH(CH₃)₂ 38(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropane-carbothioamide; mp155-156° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S: C, 56.98; H, 5.84; N, 11.07.Found: C, 56.98; H, 5.85; N, 10.97

39 (S)—N-[[3-[3,5-Difluoro-4-(4-morpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide R = F, R′ = CH₃ 40(S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)-phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′- dimethylthiourea R = H, R′ =N(CH₃)₂ PREPARATION Z Methyl Dithiopropionate

[0807] A stirred mixture of magnesium turnings (12.6 g, 0.520 g atom)and THF (100 mL) under nitrogen is treated with a crystal of iodine andabout 5% of a solution of bromoethane (30.0 mL, 0.40 mol) in THF (200mL). When the reaction starts, the remainder of the bromoethane solutionis added, dropwise at a rate sufficient to maintain a gentle reflux.After the addition, stirring is continued for 1 hour; the resultingsolution is cooled to −20° C. and treated, during 10 minutes with carbondisulfide (24.0 mL, 0.40 mol). The mixture is warmed to 15° C., treatedwith methyl iodide (28.0 mL, 0.45 mol) and kept at 60° C. for 1 hour. Itis then cooled in an ice bath, treated with ice and extracted with Et₂O.The extract is washed with brine, dried (MgSO₄) and concentrated.Distillation of the residue gives 34.0 g of the titled product, bp48-52° C. (12 mmHg).

[0808] The following methyl dithio compounds were obtained when theappropriate alkyl magnesium bromide was substituted for ethyl magnesiumbromide in the above procedure:

[0809] The following methyl dithio compounds were obtained when theappropriate alkyl magnesium bromide was substituted for ethyl magnesiumbromide in the above procedure: TABLE B

Rs = (b) (CH₃)₂CH— (h)

(c)

(i)

(d) CH₃CH₂CH₂— (j)

(e)

(k)

(f)

(l)

(g) (CH₃)₃C—CH₂— (m)

[0810] When following the general procedure of Example 27, step 4, anappropriate amount of the amine listed below is reacted with the dithiocompound listed below the respective compounds, Examples 41 to 61 ofTable C are obtained.

[0811] When following the general procedure of Example 25, step 6, anappropriate amount of the amine listed below is reacted with the dithiocompound listed below, the respective compounds, Examples 62 to 67, ofTable C are obtained. TABLE C Example Dithio Compound No. Compound Amine(from Preparation Z) 41 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholineS-oxide; mp 196-197° C.; #Anal. calcd for C₁₇H₂₂FN₃O₃S₂: C, 51.11; H,5.55; N, 10.52; S, 16.05. Found: C, 50.99; H, 5.60; N, 10.55; S, 15.75

Z(a) 42 (S)—N-[[3-[3-Fluoro-4-(4- thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholineS-oxide; mp 195-196° C.; #Anal. calcd for C₁₈H₂₄FN₃O₃S₂: C, 52.28; H,5.85; N, 10.16; S, 15.51. Found: C, 52.24; H, 5.97; N, 10.16; S, 15.28

Z(b) 43 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholineS-oxide; mp 109-110° C.; Anal. calcd for #C₁₈H₂₂FN₃O₃S₂: C, 52.54; H,5.39; N, 10.21; S, 15.58. Found: C, 52.48; H, 5.51; N, 10.28; S, 15.29

Z(c) 44 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide, thiomorpholine S-oxide

Z(d) 45 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide, thiomorpholine S-oxide

Z(e) 46 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide, thiomorpholine S-oxide

Z(f) 47 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide, thiomorpholineS-oxide

Z(g) 48 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothio- amide, thiomorpholineS-oxide

Z(h) 49 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide, thiomorpholineS-oxide

Z(i) 50 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarbothio- amide, thiomorpholineS-oxide

Z(j) 51 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethio- amide, thiomorpholineS-oxide

Z(k) 52 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclobutylethanethio- amide, thiomorpholineS-oxide

Z(l) 53 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethio- amide, thiomorpholineS-oxide

Z(m) 54 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 55 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholineS-oxide

Z(a) 56 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide

Z(b) 57 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholineS-oxide

Z(c) 58 (S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 59 (S)—N-[[3-[4-(4- thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholineS-oxide

Z(a) 60 (S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholine S-oxide

Z(b) 61 (S)—N-[[3-[4-(4- thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholineS-oxide

Z(c) 62 (S)—N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]propanethio- amide

Z(a) 63 (S)—N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-2-methyl-propanethioamide

Z(b) 64 (S)—N-[[3-[3,5-Difluoro- 4-(4-hydroxyacetyl)-1-piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]cyclopropane-thioamide

Z(c) 65 (S)—N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethio- amide

Z(a) 66 (S)—N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide

Z(b) 67 (S)—N-[[3-[3-[4- (hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide

Z(c)

[0812] When following the procedure of Example 28, step 3, anappropriate amount of the amine listed below is reacted with the dithiocompound listed below, the respective compounds, Examples 68 to 78 ofTable D are obtained. TABLE D Example Dithio Compound No. Compound Amine(see Preparation Z) 68 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholineS,S- dioxide

Z(a) 69 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholineS,S-dioxide

Z(b) 70 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholineS,S-dioxide

Z(c) 71 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide

Ethyl dithioacetate 72 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholineS,S- dioxide

Z(a) 73 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiomorpholineS,S-dioxide

Z(b) 74 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiomorpholineS,S-dioxide

Z(c) 75 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]thioacetamide, thiomorpholine S,S- dioxide

Ethyl dithioacetate 76 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethio- amide, thiomorpholineS,S-dioxide

Z(a) 77 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide, thiomorpholineS,S- dioxide

Z(b) 78 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide, thiomorpholineS,S- dioxide

Z(c)

[0813] When following the procedure of Example 26, an appropriate amountof the amine listed below is reacted with the dithio compound listedbelow the respective compounds, Examples 79 to 99 of Table E areobtained. TABLE E Example Dithio Compound No. Compound Amine (SeePreparation Z) 79 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z(a) 80 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide

Z(b) 81 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide

Z(c) 82 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide

Z(d) 83 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide

Z(e) 84 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide

Z(f) 85 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide

Z(g) 86 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclobutanecarbothio- amide

Z(h) 87 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopentanecarbothio- amide

Z(i) 88 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarbothio- amide

Z(j) 89 (S)—N-[[3-[3-5 Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopropylethanethio- amide

Z(k) 90 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclobutylethanethio- amide

Z(l) 91 (S)—N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- cyclopentylethanethio- amide

Z(m) 92 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide

Ethyl dithioacetate 93 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide

Z(a) 94 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide

Z(b) 95 (S)—N-[[3-[3,5-Difluoro- 4-(4-thiomorpholinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide

Z(c) 96 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]thioacetamide

Ethyl dithioacetate 97 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethio- amide

Z(a) 98 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-2-methyl- propanethioamide

Z(b) 99 (S)—N-[[3-[4-(4-thio- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]cyclopropane- carbothioamide

Z(c)

[0814] The amine utilized in Examples 41 to 53 is prepared as describedin Example 27, step 3. The amine utilized in Examples 54 to 57 isprepared by the procedure of Example 27, steps 1 to 3 by substitutingthe appropriate(S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanolfor compound 62 in step 1 of Example 27.

[0815] The amine utilized in Examples 58 to 61 is prepared by theprocedure of Example 27, steps 1 to 3 by substituting the appropriate(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanolfor compound 62 in Example 27, step 1. The appropriate oxazolidinylmethanol compound is obtained by following the procedure of Example 1 inU.S. Pat. No. 5,688,792, steps 1 through 3, only substituting4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.

[0816] The amine utilized in Examples 62 to 64 is prepared as compound37 in Example 29 from the amide, 65, which is prepared as described inExample 32 of U.S. Pat. No. 5,700,799. The amine utilized in Examples 65to 67 is prepared by the general procedure of Example 29 from thefollowing amide, the preparation of which is decribed in Example 3 ofU.S. Pat. No. 5,700,799:

[0817] The amine utilized in Examples 68 to 70 is prepared as describedin step 2 of Example 28 above.

[0818] The amine utilized in Examples 71 to 74 is prepared as describedin Example 28 by substituting(S)-N-[[3-[3,5-difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methanolfor compound 62 in step 1 and following the procedure of steps 1 and 2.The appropriate oxazolidinyl methanol compound is prepared by followingthe general procedure of Example 4 of U.S. Pat. No. 5,688,792, steps 1through 4, only substituting thiomorpholine for morpholine in step 1thereof.

[0819] The amine utilized in Examples 75 to 78 is prepared as describedin Example 28, step 1, above by substituting(S)-N-[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5oxazolidinyl]methanol forcompound 62 in step 1. The appropriate oxazolidinyl methanol is obtainedby following the procedure of Example 1 in U.S. Pat. No. 5,688,792,steps 1 through 3, only substituting 4-fluoronitrobenzene for3,4-difluoronitrobenzene in step 1 thereof.

[0820] The amine utilized in Examples 79 to 91 is prepared as describedin Example 1, step 4, of U.S. Pat. No. 5,688,792. The amine utilized inExamples 92 to 95 is prepared as described in Example 4 of U.S. Pat. No.5,688,792 only substituting thiomorpholine for morpholine in step 1thereof. The amine utilized in Examples 96 to 99 is prepared by theprocedure of Example 1 of U.S. Pat. No. 5,688,792, only substituting4-fluoronitrobenzene for 3,4-difluoronitrobenzene in step 1 thereof.

EXAMPLE 100(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiomorpholine S-oxide

[0821]

[0822] A solution of 201 mg (0.554 mmol) of(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanate,thiomorpholine s-oxide compound 82 from Example 33, step 1, in methanol(10 mL) is refluxed, under nitrogen for 18 hours and cooled. The solidis collected by filtration to give 0.138 g of the titled product. m.p.208-209° C.; Anal. calcd for C₁₆H₂₀FN₃O₄S₂: C, 47.87; H, 5.02; N, 10.47.Found: C, 47.81; H, 5.04: N, 10.49.

[0823] When in the procedure of Example 100 the thioisocyanate listedbelow is substituted for compound 82 the products listed below asExamples 101 to 109 are obtained. TABLE F Isothiocyanate

Ex- ample Rc Ra Rb No. Compound OS F F 101 (S)—N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthio-carbamate, thiomorpholine S-oxide OS H H 102(S)-N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thio-carbamate, thiomorpholineS-oxide O₂S H F 103 (S)—N-[[3-[3-Fluoro-4-(4-thiomorpho-linyl)-phenyl]-2-oxo-5-oxazolidinyl]meth- yl]-O-methylthiocarbamate,thio- morpholine S,S-dioxide O₂S F F 104 (S)—N-[[3-[3,5-Difluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthio-carbamate, thiomorpholin S,S-dioxide O₂S H H 105(S)—N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate, thiomorpholineS,S-dioxide S H F 106 (S)—N-[[3-[3-Fluoro-4-(4-thio-morpholinyl)-phenyl]-2-oxo-5-oxa-zolidinyl]methyl]-O-methylthiocarbamate S F F 107(S)—N-[[3-[3,5-Difluoro-4-(4-thiomorph-olinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate S HH 108 (S)—N-[[3-[4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate

H H 109 (S)—N-[[3-[3-Fluoro- 4-(4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate

[0824] When in the procedure of Example 100 an appropriate amount ofethanol and isopropyl alcohol were substituted for methanol, thefollowing respective compounds were obtained:

[0825] EXAMPLE 110:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiomorpholine S-oxide. m.p. 198-199° C.; Anal. calcd for C₁₇H₂₂FN₃O₄S₂:C, 49.14; H, 5.34; N, 10.11. Found: C, 49.06; H, 5.27; N, 10.10.

[0826] EXAMPLE 111:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiomorpholine S-oxide. m.p. 180-181° C.; Anal. calcd for C₁₈H₂₄FN₃O₄S₂:C, 50.33; H, 5.63; N, 9.78. Found: C, 50.29; H, 5.69; N, 9.82.

[0827] When in the procedure of Example 114 an appropriate amount of(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]isothiocyanateis substituted for compound 82 and ethanol or isopropyl alcohol issubstituted for methanol, the following respective products areobtained:

[0828] EXAMPLE 112:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;

[0829] EXAMPLE 113:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate;

[0830] EXAMPLE 114:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]N-methylthiourea,thiomorpholine S-oxide.

[0831] A stirred suspension of 240 mg (0.650 mmol) of compound 82 fromExample 33, step 1 in THF (5 mL) at 0° C. is treated with a 2M solutionof methylamine in THF (0.42 mL, 0.845 mmol) and kept at ambienttemperature for 18 hours. The solid is collected by filtration to give0.221 g of the titled product.

[0832] Following the procedure of Example 114, only substituting anappropriate amount of dimethylamine and azetidine for methylamine, thefollowing compounds are obtained:

[0833] EXAMPLE 115:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]N′,N′-dimethylthiourea,thiomorpholine S-oxide; Anal. Calcd for C₁₇H₂₃FN₄O₃S₂, C, 49.26; H,5.59; N, 13.52. Found C, 49.11; H, 5.57; N, 13.40; mp 180-182° C.

[0834] EXAMPLE 116:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiomorpholine S-oxide; Anal. Calcd for C₁₈H₂₃FN₄O₃S₂, C, 50.69; H,5.43; N, 13.14. Found: C, 50.79; H, 5.45; N, 12.82; mp 213-214° C.

[0835] When in the procedure of Example 114 an appropriate amount of(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanateis substituted for compound 82, the following compound is obtained:

[0836] EXAMPLE 117:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methyl-N′-methylthiourea.

[0837] When in the procedure of Example 117 an appropriate amount ofdimethylamine and azetidine are substituted for methylamine, thefollowing respective products are obtained:

[0838] EXAMPLE 118:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;

[0839] EXAMPLE 119:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide.

[0840] When in the procedure of Example 33 an appropriate amount ofcompound 31 from Example 26 is substituted for compound 33 and thegeneral procedure of steps 1 and 2 of Example 33 are followed, thefollowing compound is obtained.

[0841] EXAMPLE 120:(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea.

[0842] EXAMPLE 121:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]propanethioamide

[0843] A stirred mixture of 200 mg (0.514 mmol) of 29 methyldithiopropionate (247 mg, 2.06 mmol), triethylamine (0.58 mL, 4.11mmol), THF (5.4 mL) and methylene chloride (5.4 mL) is kept, undernitrogen, for 3 days, diluted with water and extracted with methylenechloride. The extracts are dried (MgSO₄) and concentrated.Chromatography of the residue on silica gel and crystallization of theproduct from methanol gives 0.132 g of the titled product. m.p. 190-191°C.; Anal. calcd for C₁₉H₂₅FN₄O₄S: C, 53.76; H, 5.94; N, 13.20; S, 7.55.Found: C, 53.66; H, 5.94; N, 13.20; S, 7.37.

[0844] Following the procedure of Example 121 only substituting dithiocompounds Z (b) to Z (m) from Preparation Z above for methyldithiopropionate, the following compounds are obtained. TABLE G

Ex- ample No. Compound 122 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- R =CH(CH₃)₂ acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide; Anal. calcd forC₂₀H₂₇FN₄O₄S: C, 54.78; H, 6.21; N, 12.78; S, 7.31. Found: C, 54.67; H,6.34; N, 12.41; S, 7.15 123 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropane-carbothioamide; mp 179-181° C.; Anal. calcd for C₂₀H₂₅FN₄O₄S: C, 55.03;H, 5.77; N, 12.84; S, 7.34. Found: C, 55.15; H, 5.72; N, 12.76; S, 7.09

124 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- R = CH₂—CH₂—CH₃acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]butanethioamide 125(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutane- thioamide

126 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutane- thioamide

127 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy- R = CH₂—C(CH₃)₃acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethyl- butanethioamide 128(S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclobutane-carbothioamide

129 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopentane-carbothioamide

130 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclohexane-carbothioamide

131 (S)—N-[[3-[3-Fluoro-4-[4-hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropyl- ethanethioamide

132 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutyl- ethanethioamide

133 (S)—N-[[3-[3-Fluoro-4-[4-(hydroxy-acetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentyl- ethanethioamide

[0845] When in the procedure of Example 100 an appropriate amount ofcompound 80 from Example 31 is substituted for compound 82, and ethanolor isopropyl alcohol is substituted for methanol, the followingrespective compounds are obtained:

[0846] EXAMPLE 134:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;

[0847] EXAMPLE 135:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-iso-propylthiocarbamate;

[0848] EXAMPLE 136:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea.

[0849] When in the procedure of Example 114 an appropriate amount ofcompound 80 from Example 31 is substituted for compound 82, the titlecompound is obtained.

[0850] Following the procedure of Example 114 only substituting anappropriate amount of compound 80 from Example 31 for compund 82 andsubstituting an appropriate amount of dimethylamine and azetidine formethylamine, the following compounds, Examples 137 and 138, areobtained:

[0851] EXAMPLE 137:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea;

[0852] EXAMPLE 138:(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide.

EXAMPLE 139(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate.

[0853] Part A: Following the procedure of Example 33, step 1, onlysubstituting an appropriate amount of compound 37 from Example 29, step5, for compound 33,(S)-N-[[3,5-[3-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanateis obtained.

[0854] Part B: Upon substitution of an appropriate amount of(S)-N-[[3-[3,5-difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanatefor compound 82 in the general procedure of Example 100, the titlecompound is obtained.

EXAMPLE 140(S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate

[0855] Part A: Following the procedure of Example 33, step 1, onlysubstituting an appropriate amount of(S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]aminefor compound 33,(S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanateis obtained.

[0856] Part B: Upon substituting an appropriate amount of(S)-N-[[3-[4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]isothiocyanatefor compound 82 in the general procedure of Example 100, the titlecompound is obtained.

EXAMPLE 141(S)-N-[[-3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

[0857]

[0858] An ice cold, stirred solution of 30.4 g (70.8 mmol) of startingmaterial 58 from Example 25, step 1), and triethylamine (15.4 mL, 110mmol) in methylene chloride (2570 mL) is treated withm-nitrobenzenesulfonyl chloride (18.8 g, 84.9 mmol) and kept, undernitrogen, at ambient temperature (24° C.) for 24 hours. Additionalm-nitrobenzenesulfonyl chloride (1.88 g) and triethylamine (1.54 mL) areadded and the mixture is kept for one additional day at ambienttemperature, washed with water, saturated sodium bicarbonate and brine,dried (Na₂SO₄) and concentrated to give an oily product, 85. Thealcohol, 58 is prepared according to the procedures of Brickner (J. Med.Chem. 1996, 39, 673-679), see compound 5a therein.

[0859] A stirred mixture of 85, acetonitrile (1270 mL), isopropanol(1270 mL) and ammonium hydroxide (1270 mL) is kept at ambienttemperature for 3 days and concentrated in vacuo. Chromatography of theresidue on silica gel with 0.5% NH₄OH-1% MeOH—CH₂Cl₂ gives 22.4 g of theamine, 86.

[0860] An ice cold, stirred solution of the amine 86 in THF (650 mL) istreated, during 20 mintues with a solution of di-tert-butyl dicarbonate(12.0 g, 55.2 mmol) in THF (90 mL). The mixture is kept at ambienttemperature for 18 hours and concentrated in vacuo. The residue,dissolved in methylene chloride, is washed with dilute sodiumbicarbonate, dried (MgSO₄) and concentrated. Crystallization of theresidue from methanol-ethyl acetate gives 20.0 g of the Boc protectedamine. Additional product (4.1 g) is obtained by chromatographing themother liquors on silica gel with 1-2% methanol-methylene chloride.

[0861] A solution of the protected amine, 87, (5.00 g, 9.46 mmol) inethanol (150 mL) is treated with 10% palladium-on-carbon catalyst (1.0g) and hydrogenated at an initial pressure of 30 psi for 3 hours. Thecatalyst is removed by filtration through Celite and the filtrate wasconcentrated to give 3.66 g of compound 88.

[0862] A stirred solution of compound 88 (1.10 g, 2.79 mmol) in pyridine(10 mL) is treated with acetic anhydride (289 μL, 3.07 mmol), kept atambient temperature for 2 hours and concentrated in vacuo. A solution ofthe residue in methylene chloride is washed with dilute hydrochloricacid, dried (MgSO₄) and concentrated to give 1.23 g of compound 89: MSm/z 436 (M⁺).

[0863] An ice cold, stirred 4N solution of HCl in dioxane (10 mL) istreated with compound 89 (1.10 g, 2.52 mmol). The mixture is kept in theice bath for 30 minutes and at ambient temperature for 1 hour. It wasthen mixed with methylene chloride and concentrated. The residue istriturated with methylene chloride to give 1.03 g of the aminehydrochloride.

[0864] A stirred mixture of compound P-90 (250 mg), triethylamine (0.75mL, 5.36 mmol), ethyl dithioacetate (307 μL, 2.68 mmol), methylenechloride (7.4 mL) and THF (7.4 mL) is kept at ambient temperature for 1day, concentrated and chromatographed on silica gel with mixtures ofmethanol-methylene chloride containing 1-2% methanol. Crystallization ofthe product from ethyl acetate-heptane gives 0.160 g of the titledproduct: Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20; S,8.13. Found: C, 54.92; H, 5.95; N, 14.08; S, 7.94; mp 158° C.

[0865] When in the general procedure of Example 141 an appropriateamount of

[0866] is substituted for compound 58 and the procedure of steps 1through 6 are followed, the respective amine compounds P-91 and P-92listed below are obtained:

[0867] The alcohols above designated as x and y are prepared accordingto the procedures of Brickner (J. Med. Chem., 1996, 39, 673-679), bysubstituting an appropriate amount of 2,6-difluoro-4-nitrobenzene(trifluoromethane) sulfonate and 4-fluoronitrobenzene respectively for3,4-difluoronitrobenzene in the preparation of 2a therein.

[0868] When in the procedure of Example 141 an appropriate amount of xor y is substituted for compound 58 and the procedures of steps 1through 4 are followed, the following Boc protected compounds listedbelow are obtained.

[0869] When in the procedure of Example 141, step 5, an appropriateamount of compound 88, compound x-b or compound y-b is treated with thereagent listed below and the general procedures of step 5 and step 6 arefollowed, the amines listed below as Preparation P-93 through P-128 areobtained.

[0870] The amine compound set forth below as P-129 is obtained byrefluxing for 6 days a solution of compound 88 (1.00 g, 2.54 mmol),sulfamide (305 mg, 3.18 mmol) and 1,2-dimethyoxyethane (6 mL). The solidwhich precipitates is collected by filtration and chromatographed onsilica gel with 5% methanol-methylene chloride. Crystallization of theproduct from methanol-methylene chloride gives 0.551 g of the sulfamoylderivative, which is used in step 6 of Example 141 to give P-129. Whencompounds x-b and y-b are substituted for compound 88 and this generalprocedure is followed, Preparations P-130 and P-131 respectively setforth below are obtained.

[0871] Following the general procedures of steps 5 and 6 of Example 141only in step 5 substituting chloroacetonitrile or 2-fluoroethyl bromiderespectively for acetic anhydride and using potassium carbonate inacetonitrile, and using either compound 88, compound x-b or compoundy-b, the respective amines set forth below as Preparations P-132 toP-137 are obtained.

[0872] The amine compound set forth below as Preparation P-138 isobtained by combining compound 88 (1.10 g, 2.75 mmol) set forth in step5 of Example 141 with N-formylbenzotriazole (493 mg, 3.35 mmol) in THF(30 mL) and the mixture is kept at ambient temperature for 18 hours. Themixture is concentrated and the residue in methylene chloride is washedwith 1N sodium hydroxide and dilute sodium chloride, dried (MgSO₄),concentrated, and chromatographed on silica gel with mixtures ofmethanol and methylene chloride containing 1-2% methanol to give 1.09 gof the N-formyl derivative which is utilized in the general procedure ofstep 6 of Example 141 to give Preparation P-138. When in this foregoingprocedure compound x-b or compound y-b is substituted for compound 88,Preparations P-139 and and P-140 as set forth below are obtained.

Boc Preparation Reagent Compound R R″ R′ No. methoxyacetylchloride 88x-b y-b

H F H F F H P-93 P-94 P-95 cyanoacetyl chloride 88 x-b y-b

H F H F F H P-96 P-97 P-98 acetoxyacetyl chloride 88 x-b y-b

H F H F F H P-99 P-100 P-101 benzyloxyacetyl chloride 88 x-b y-b

H F H F F H P-102 P-103 P-104 methyl chloroformate 88 x-b y-b

H F H F F H P-105 P-106 P-107 methanesulfonyl chloride 88 CH₃SO₂— H FP-108 x-b F F P-109 y-b H H P-110 ethanesulfonyl chloride 88 CH₃CH₂SO₂—H F P-111 x-b F F P-112 y-b H H P-113 chloromethaneslfonyl 88 ClCH₂SO₂—H F P-114 chloride x-b F F P-115 y-b H H P-116 cyanomethanesulfonyl 88NCCH₂SO₂— H F P-117 chloride x-b F F P-118 y-b H H P-119N-methylsulfamoyl 88 CH₃NHSO₂— H F P-120 chloride x-b F F P-121 y-b H HP-122 N,N-dimethylsulfamoyl 88 (CH₃)₂NSO₂— H F P-123 chloride x-b F FP-124 y-b H H P-125 ethyl chloroformate 88 x-b y-b

H F H F F H P-126 P-127 P-128 sulfamide 88 H₂NSO₂— H F P-129 x-b F FP-130 y-b H H P-131 chloroacetonitrile 88 NCCH₂— H F P-132 x-b F F P-133y-b H H P-134 2-fluoroethyl bromide 88 FCH₂CH₂— H F P-135 x-b F F P-136y-b H H P-137 N-formylbenzotriazole 88 x-b y-b

H F H F F H P-138 P-139 P-140

EXAMPLES 142-161

[0873] When following the general procedures of Example 141, step 7, anappropriate amount of the amine listed below and the dithio compoundfrom Preparation Z listed below are utilized, the respective productsdesignated as Examples 142 to 400 in Table H are obtained. TABLE HExample Dithio No. Product Amine Compound 142(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (a)2-oxo-5-oxazolidinyl]methyl]propanethioamide; mp 161-162° C.; Anal.calcd for C₁₉H₂₅FN₄O₃S: C, 55.87; H, 6.17; N, 13.72; S, 7.85. Found: C,55.79; H, 6.26; N, 13.60; S, 7.71 143(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (b)2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 144(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (c)2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbo- thioamide; mp 159-160°C.; Anal. calcd for C₂₀H₂₅FN₄O₃S: C, 57.13; H, 5.99; N, 13.32; S, 7.62.Found: C, 57.05; H, 6.01; N, 13.15; S, 7.45. 145(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (d)2-oxo-5-oxazolidinyl]methyl]butanethioamide 146(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (e)2-oxo-5-oxazolidinyl]methyl]-3-methylbutane- thioamide 147(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (f)2-oxo-5-oxazolidinyl]methyl]-2-methylbutane- thioamide 148(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (g)2-oxo-5-oxazolidinyl]methy;]-3,3-dimethylbutane- thioamide 149(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (h)2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbo- thioamide 150(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (i)2-oxo-5-oxazolidinyl]methyl]cyclopentanecarbo- thioamide 151(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (j)2-oxo-5-oxazolidinyl]methyl]cyclohexanecarbo- thioamide 152(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (k)2-oxo-5-oxazolidinyl]methy;]-2-cyclopropylethane- thioamide 153(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (l)2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethane- thioamide 154(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]- P-90  Z (m)2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethane- thioamide 155(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91  Ethylphenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 156(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91  Z (a)phenyl]-2-oxo-5-oxazolidinyl]methyl]propane- thioamide 157(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91  Z (b)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 158(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1-piperazinyl)- P-91  Z (c)pjhenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 159(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92  Ethyloxazolidinyl]methyl]thioacetamide dithio- acetate 160(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92  Z (a)oxazolidinyl]methyl]propanethioamide 161(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92  Z (b)oxazolidinyl]methyl]-2-methylpropanethioamide 162(S)-N-[[3-[4-(4-Acetyl-1-piperazinyl)phenyl]-2-oxo-5- P-92  Z (c)oxazolidinyl]methyl]cyclopropanecarbothioamide 163(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 164 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 165(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 166 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-P-93  Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothiamide 167(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (d)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 168(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (e)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide 169 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-P-93  Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide 170 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-P-93  Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide 171 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1-P-93  Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclobutanecarbothioamide 172(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (i)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopentanecarbothioamide 173(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (j)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclohexanecarbothioamide 174(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (k)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide 175(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (l)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide 176(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  Z (m)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 177(S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1- P-94  Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 178 (S)-N-[[3-[3,5-Dilfuooro[4-[4-(methoxyacetyl)-1- P-94  Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 179(S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxyacetyl)-1- P-94  Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 180(S)-N-[[3-[3,5-Difluoro[4-[4-(methoxyacetyl)-1- P-94  Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 181(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95  Ethyl2-oxo-5-oxazolidinyl]methyl]thioacetamide 182(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95  Z (a)2-oxo-5-oxazolidinyl]methyl]propanethioamide 183(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95  Z (b)2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 184(S)-N-[[3-[4-[4-(methoxyacetyl)-1-piperazinyl]phenyl]- P-95  Z (c)2-oxo-5- oxazolidinyl]methyl]cyclopropanecarbothioamide 185(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96  Ethylphenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 186(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96  Z (a)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethio- amide 187(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96  Z (b)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 188(S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)-1-piperazinyl]- P-96  Z (c)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothiamide 189(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97  Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- dithio- methyl]thioacetamideacetate 190 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97  Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethioamide 191(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1- P-97  Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 192 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanoacetyl)-1-P-97  Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]cyclopropanecarbothioamide 193(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98  Ethyloxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 194(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98  Z (a)oxo-5-oxazolidinyl]methyl]propanethioamide 195(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98  Z (b)oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 196(S)-N-[[3-[4-[4-(Cyanoacetyl)-1-piperazinyl]phenyl]-2- P-98  Z (c)oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio- amide 197(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide 198(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 199(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 200 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-P-99  Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 201(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (d)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 202(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (e)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide 203 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-P-99  Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide 204 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-P-99  Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide 205 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-P-99  Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclobutanecarbothioamide 206(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (i)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopentanecarbothioamide 207(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (j)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclohexanecarbothioamide 208(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (k)piperazinyl]phenyl]-2-oxo-5-oxazlidinyl]methyl]-2-cyclopropylethanethioamide 209(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (l)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide 210(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  Z (m)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 211(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide 212(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 213(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 214(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxyacetyl)-1- P-100 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 215(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Ethyl2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 216(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Z (a)2-oxo-5-oxazolidinyl]methyl]propanethioamide 217(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Z (b)2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 218(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1-piperazinyl]phenyl]- P-101 Z (c)2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbo- thioamide 219(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 220 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 221(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanecarbothioamide 222(S)-N-[[3-[3-Fluoro-4-[4-(benzyloxyacetyl)-1- P-102 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 223(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 224 (S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide225 (S)-N-[[3-[3,5-Difluoro-4-[4-benzyloxyacetyl)-1- P-103 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 226(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxyacetyl)-1- P-103 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 227(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 228 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 229(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 230 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-P-105 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 231(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (d)piperazinyl]phenyl]-2-oxo-5-oxazlidinyl]methyl]- butanethioamide 232(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (e)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide 233 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-P-105 Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide 234 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1-P-105 Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide 235(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (h)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclobutanecarbothioamide 236(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (i)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopentanecarbothioamide 237(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (j)piperazinyl]phenyl]-2-oxo-5-oxaolidinyl]methyl]-cyclohexanecarbothioamide 238(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (k)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide 239(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (l)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanethioamide 240(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)-1- P-105 Z (m)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 241(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 242 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide243 (S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Z (b)piperazinyl]phenyl]-2-oxo-5-oxaolidinyl]methyl]-2-methylpropanethioamide 244(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxycarbonyl)-1- P-106 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 245 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1-P-107 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio-thioacetamide acetate 246 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide247 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 248 (S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 Z(c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 249(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide;mp 197-198° C.; Anal. calcd for acetate C₁₇H₂₃FN₄O₄S₂: C, 47.43; H,5.39; N, 13.01; C, 14.89. Found: C, 47.25; H, 5.40; N, 12.82; S, 14.56.250 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide; mp207-208° C.; Anal. calcd for C₁₈H₂₅FN₄O₄S₂: C, 48.63; H, 5.67; N, 12.60;S, 14.42. Found: C, 48.51; H, 5.59; N, 12.52; S, 14.09. 251(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide; mp 204-206° C.; Anal. calcd for C₁₉H₂₇FN₄O₄S₂:C, 49.76; H, 5.93; N, 12.22; S, 13.98. Found: C, 49.63; H, 5.92; N,14.14; S, 13.91. 252 (S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1- P-108Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide; Anal. calcd for C₁₉H₂₅FN₄O₄S₂: C, 49.98; H,5.52; N, 12.27; S, 14.04. Found: C, 49.42; H, 5.50; N, 12.08; S, 13.80.253 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 254 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide255 (S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 256(S)-N-[[3-[3,5-Difluoro-4-[4-(methanesulfonyl)-1- P-109 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 257 (S)-N-[[3-[4-[4-(methanesulfonyl)-1-P-110 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio-thioacetamide 258 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 259(S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 260 (S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 Z(c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 261(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 262 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 263(S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1- P-111 Z (b)piperazinyl]phenyl]-2-oxo-5-exazolidinyl]methyl]-2-methylpropanethioamide 264 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)-1-P-111 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopeopanecarbothioamide 265(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 266 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 267(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 268(S)-N-[[3-[3,5-Difluoro-4-[4-(ethanesulfonyl)-1- P-112 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 269(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Ethyl2-oxo-5-oxazolifinyl]methyl]thioacetamide dithio- acetate 270(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Z (a)2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 271(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Z (b)2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide 272(S)-N-[[3-[4-[4-(ethanesulfonyl)-1-piperazinyl]phenyl]- P-113 Z (c)2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio- amide 273(S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 274 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide275 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 276(S)-N-[[3-[3-Fluoro-4-[4-(chloromethanesulfonyl)-1- P-114 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 277(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Ethyl1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio-thioacetamide acetate 278(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Z (a)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 279(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Z (b)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 280(S)-N-[[3-[3,5-Difluoro-4-[4-(chloromethanesulfonyl)- P-115 Z (c)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 281(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide282 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 283(S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1- P-116 Z (b)piperazinyl]phenyl]-2-oxo-5-pxazolidinyl]methyl]-2-methylpropanethioamide 284 (S)-N-[[3-[4-[4-(chloromethanesulfonyl)-1-P-116 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 285(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 286 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide287 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Z (b)piperazinyl]phenyl]020oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 288(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane-sulfonyl)-1- P-117 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 289(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Ethyl1-piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 290 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118Z (a) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]propanethioamide 291(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Z (b)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 292(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethane-sulfonyl)- P-118 Z (c)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 293 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1-P-119 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio-oxazolidinyl]methyl]thioacetamide acetate 294(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 Z (a)piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 295(S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1- P-119 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 296 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)-1-P-119 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide 297(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfomaoyl)-1- P-120 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 298 (S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 299(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 300(S)-N-[[3-[3-Fluoro-4-[4-(N-methylsulfamoyl)-1- P-120 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 301(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 302 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide303 (S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 304(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methylsulfamoyl)-1- P-121 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 305 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1-P-122 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio-thioacetamide acetate 306 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide307 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 308 (S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 309(S)-N-[[3-[30Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 310 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Z(a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide311 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 312(S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethylsulfamoyl)-1- P-123 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 313(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Ethyl1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio-thioacetamide 314 (S)-N-[[3-[3,5-Difluoro-4-[4-(N,Ndimethylsulfamoyl)-P-124 Z (a) 1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-propanethioamide 315(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Z (b)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 316(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-dimethylsulfamoyl)- P-124 Z (c)1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 317(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 318 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 319(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1- P-125 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 320 (S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)-1-P-125 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 321(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- thioacetamide 322(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 323(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 324 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-P-126 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 325(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (d)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- butanethioamide 326(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (e)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide 327 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-P-126 Z (f) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide 328 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-P-126 Z (g) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide 329 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1-P-126 Z (h) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclobutanecarbothioamide 330(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (i)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopentanecarbothioamide 331(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (j)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclohexanecarboamide332 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (k)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropylethanethioamide 333(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (l)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclobutylethanthioamide 334(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 Z (m)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 335(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamide336 (S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 337(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 338(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxycarbonyl)-1- P-127 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 339(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Ethylphenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 340(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Z (a)phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 341(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Z (b)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 342(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1-piperazinyl]- P-128 Z (c)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 343(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Ethylphenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 344(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Z (a)phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 345(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Z (b)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 346(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-piperazinyl)- P-129 Z (c)phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 347(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (d)piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]butanethioamide 348(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (e)piper4azinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3-methylbutanethioamide 349 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z(f) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylbutanethioamide 350 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z(g) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-3,3-dimethylbutanethioamide 351 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129Z (h) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclobutanecarbothioamide 352(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (h)piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopentanecarbothioamide 353(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (j)piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclohexanecarbothioamide 354(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (k)piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopropylethanethioamide 355 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-P-129 Z (l) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- 356(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 Z (m)piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-cyclopentylethanethioamide 357 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-P-130 Ethyl piperazinyl)phenyl]-2-oxo-5- dithio-oxazolidinyl]methyl]thioacetamide acetate 358(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 Z (a)piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 359(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 Z (b)piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 360 (S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1-P-130 Z (c) piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide 361(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Ethyl5-oxazolidinyl]methyl]thioacetamide dithio- acetate 362(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Z (a)5-oxazolidinyl]methyl]propanethioamide 363(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Z (b)5-oxazolidinyl]methyl]-2-methylpropanethioamide 364(S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)phenyl]-2-oxo- P-131 Z (c)5-oxazolidinyl]methyl]cyclopropanecarbothioamide 365(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide366 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Z (a)piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 367(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 368 (S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1-P-132 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide 369(S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1- P-133 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 370 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1- P-133 Z (a)piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 371(S)-N-[[3-[3,5-Difluoro-4-[4 cyanomethyl)-1- P-133 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 372 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyanomethyl)-1-P-133 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 373(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2- P-134 Ethyloxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 374(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2- P-134 Z (a)oxo-5-oxazolidinyl]methyl]propanethioamide 375(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]-2- P-134 Z (b)oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 376(S)-N-[[3-[4-[4-(cyanomethyl)-1-piperazinyl]phenyl]- P-134 Z (c)2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 377(S)-N-[[3-[3-Fluoro-4-[3-(2-fluoroethyl)-1- P-135 Ethylpiperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamideacetate 378 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 Z (a)piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 379(S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 380 (S)-N-[[3-[3-Fluoro-4-[43-(2-fluoroethyl)-1-P-135 Z (c) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 381(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Ethylpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- dithio- thioacetamideacetate 382 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Z (a)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 383(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Z (b)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide 384(S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoroethyl)-1- P-136 Z (c)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-cyclopropanecarbothioamide 385(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Ethyl2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 386(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Z (a)2-oxo-5-oxazolidinyl]methyl]propanethioamide 387(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Z (b)2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 388(S)-N-[[3-[4-[4-(2-fluoroethyl)-1-piperazinyl]phenyl]- P-137 Z (c)2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 389(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]- P-138 Ethyl2-oxo-5-oxazolidinyl]methyl]thioacetamide; Ana calcd dithio- forC₁₇H₂₁FN₄O₃S: C, 53.67; H, 5.56; N, 14.73; S, acetate 8.43. Found: C,53.14; H, 5.42; N, 14.25; S, 8.18. 390(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]- P-138 Z (a)2-oxo-5-oxazolidinyl]methyl]propanethioamide; mp 166-167° C.; Anal.calcd for C₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20; S, 8.13. Found: C,54.83; H, 6.00; N, 14.12; S, 7.96. 391(S)-N-[[3-[3-Fluoro-4-(4-formyla-1-piperazinyl)phenyl]- P-138 Z (b)2-oxo-5-oxazolidinyl]methyl]-2-methylpropane- thioamide; mp 157-158° C.:Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87, H, 6.17; N, 13.72; S, 7.85.Found: C, 55.67; H, 6.19; N, 13.50; S, 7.70. 392(S)-N-[[3-Fluoro-4-(4-formyla-1-piperazinyl)phenyl]- P-138 Z (c)2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide; mp 178-179°C.; Anal. calcd for C₁₉H₂₃FN₄O₃S: C, 56.14; H, 5.70; N, 13.78; S, 7.89.Found: C, 56.13; H, 5.64; N, 13.64; S, 7.75. 393(S)-N-[[3-[3,5-Difluoro-4-(4-formyl-1-piperazinyl)- P-139 Ethylphenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide dithio- acetate 394(S)-N-[[3-[3,5-Difluoro-4-(4-formyl-1-piperazinyl)- P-139 Z (a)phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide 395(S)-N-[[3-[3,5-Difluoro-4-(4-formyla-1-piperazinyl)- P-139 Z (b)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methyl- propanethioamide 396(S)-N-[[3-[3,5-Difluoro-4-(4-formyla-1-piperazinyl)- P-139 Z (c)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclo- propanecarbothioamide 397(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Ethyloxazolidinyl]methyl]thioacetamide dithio- acetate 398(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Z (a)oxazolidinyl]methyl]propanethioamide 399(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Z (b)oxazolidinyl]methyl]-2-methylpropanethioamide 400(S)-N-[[3-[4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5- P-140 Z (c)oxazolinyl]methyl]cyclopropane-carbothiamide

[0874] When in the general procedure of Example 31, step 1, anappropriate amount of the amine listed below is substituted for compound33, the isothiocyanate corresponding to the amines P-90, P-93, P-99,P-105, P-126 and P-129 are obtained.

[0875] When in the general procedure of Example 114 an appropriateamount of the isothiocyanate and the amine listed below are substitutedfor compound 82 and methylamine, the respective products listed beloware obtained. TABLE I Isothiocyanate Example Corresponding No. Productto Amine No. Amine 401 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 methylamine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′-methylthiourea 402 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 dimethylamine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 403 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-P-90  azetidine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-1-azetidinecarbothioamide 404(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)- P-90  anhydrousphenyl]-2-oxo-5-oxazolidinyl]methyl]- ammonia thiourea 405(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  methylaminepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 406(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  dimethylaminepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 407(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)-1- P-93  azetidinepiperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide 408 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1-P-99  methylamine piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′-methylthiourea 409(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  dimethylaminepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 410(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)-1- P-99  azetidinepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-1-azetidinecarbothioamide 411(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 methylamine1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea412 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 dimethylamine1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 413(S)-N-[[3-[3-Fluoro-4-[4-(methoxycarbonyl)- P-105 azetidine1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-1-azetidinecarbothioamide 414(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 methylaminepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 415(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 dimethylaminepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 416(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycarbonyl)-1- P-126 azetidinepiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-1-azetidinecarbothioamide 417(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 methylaminepiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-N′-methylthiourea 418(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 dimethylaminepiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-N′,N′-dimethylthiourea 419 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-P-129 azetidine piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-1-azetidinecarbothioamide

[0876] When in the general procedure of Example 100 an appropriateamount of the isothiocyanate and alcohol listed below are utilized inthe same manner as Compound 82 and methanol are utilized, the respectiveproducts listed below are obtained. TABLE J Isothio- cyanate Ex- Corres-am- ponding to ple Amine No. Product No. Amine 420(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 methanolpiperazinyl)phenyl]2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate421 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 ethanolpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-ethylthiocarbamate422 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 isopropylpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- alcoholmethyl]-O-iso-propylthiocarbamate 423(S)-N-[[3-[3,5-Difluoro-4-(4-acetyl-1- P-91 methanolpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate424 (S)-N-[[3-[4-(4-Acetyl-1- P-92 methanolpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate425 (S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)- P-93 methanol1-piperazinyl]phenyl]-2-oxo-5-oxazoli-dinyl]-methyl]-O-methylthiocarbamate 426(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)- P-93 ethanol1-piperazinyl]phenyl]-2-oxo-5-oxazoli-dinyl]methyl]-O-ethylthiocarbamate 427(S)-N-[[3-[3-Fluoro-4-[4-(methoxyacetyl)- P-93 isopropyl1-piperazinyl]phenyl]-2-oxo-5- alcohol oxazolidinyl]-methyl]-O-iso-propylthiocarbamate 428 (S)-N-[[3-[3,5-Difluoro-[4-[4-(methoxy- P-94methyl- acetyl)-1-piperazinyl]phenyl]-2-oxo-5- amineloxazolidinyl]methyl]-O-methylthio- carbamate 429(S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 methyl-piperazinyl]phenyl]-2-oxo-5- amine oxazolidinyl]methyl]-O-methylthio-carbamate 430 (S)-N-[3-[3-Fluoro-4-[4-(cyanoacetyl)-1- P-96 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate431 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-97 methanolacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 432(S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate433 (S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)- P-99 methanol1-piperazinyl]phenyl]-2-oxo-5-oxazoli-dinyl]-methyl]-O-methylthiocarbamate 434(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)- P-99 ethanol1-piperazinyl]phenyl]-2-oxo-5-oxazoli-dinyl]-methyl]-O-ethylthiocarbamate 435(S)-N-[[3-[3-Fluoro-4-[4-(acetoxyacetyl)- P-99 isopropyl1-piperazinyl]phenyl]-2-oxo-5-oxazoli- alcoholdinyl]-methyl]-O-iso-propylthiocarbamate 436(S)-N-[[3-[3,5-Difluoro-4-[4-(acetoxy- P-100 methanolacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 437(S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P-101 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate438 (S)-N-[[3-[3-Fluoro-4-[4-(benzyloxy- P-102 methanolacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 439(S)-N-[[3-[3,5-Difluoro-4-[4-(benzyloxy- P-103 methanolacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 440(S)-N-[[3-[3-Fluoro-4-[4-(methoxycar- P-105 methanolbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 441(S)-N-[[3-[3-Fluoro-4-[4-(methoxycar- P-105 ethanolbonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]-methyl]-O-ethylthio-carbamate 442 (S)-N-[[3-[3-Fluoro-4-[4-(methoxycar- P-105 isopropylbonyl)-1-piperazinyl]phenyl]-2-oxo-5- alcoholoxazolidinyl]-methyl]-O-iso-propylthio- carbamate 443(S)-N-[[3-[3,5-Difluoro-4-[4-(methoxy- P-106 methanolcarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 444(S)-N-[[3-[4-[4-(methoxycarbonyl)-1- P-107 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate445 (S)-N-[[3-[3-Fluoro-4-[4-(methanesul- P-108 methanolfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxa-zolidinyl]-methyl]-O-methylthiocarbamate 446(S)-N-[[3-[3,5-Difluoro-4-[4-(methane- P-109 methanolsulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 447(S)-N-[[3-[4-[4-(methanesulfonyl)-1- P-110 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate448 (S)-N-[[3-[3-Fluoro-4-[4-(ethanesulfonyl)- P-111 methanol1-piperazinyl]phenyl]-2-oxo-5-oxazoli-dinyl]-methyl]-O-methylthiocarbamate 449(S)-N-[[3-[3,5-Difluoro-4-[4-(ethane- P-112 methanolsulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane- carbothioamide 450(S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P-113 methanolpiperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthio-carbamate 451 (S)-N-[[3-[3-Fluoro-4-[4-(chloromethane- P-114 methanolsulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 452(S)-N-[[3-[3,5-Difluoro-4-[4-(chloro- P-115 methanolmethanesulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate 453(S)-N-[[3-[4-[4-(chloromethanesulfonyl)- P-116 methanol1-piperazinyl]phenyl]-2-oxo-5-oxazolidi-nyl]methyl]-O-methylthiocarbamate 454(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethane- P-117 methanolsulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 455(S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-118 methanolmethane-sulfonyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate 456 (S)-N-[[3-[4-[4-(Cyanomethanesulfonyl)- P-119methanol 1-piperazinyl]phenyl]-2-oxo-5-oxazoli-dinyl]-methyl]-O-methylthiocarbamate 457(S)-N-[[3-[3-Fluoro-4-[4-(N-methyl- P-120 methanolsulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 458(S)-N-[[3-[3,5-Difluoro-4-[4-(N-methyl- P-121 methanolsulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 459(S)-N-[[3-[4-[4-(N-methylsulfamoyl)-1- P-122 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate460 (S)-N-[[3-[3-Fluoro-4-[4-(N,N-dimethyl- P-123 methanolsulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 461(S)-N-[[3-[3,5-Difluoro-4-[4-(N,N-di- P-124 methanolmethyl-sulfamoyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methyl- thiocarbamate 462(S)-N-[[3-[4-[4-(N,N-dimethylsulfamoyl)- P-125 methanol1-piperazinyl]phenyl]-2-oxo-5-oxa-zolidinyl]methyl]-O-methylthiocarbamate 463(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycar- P-126 methanolbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 464(S)-N-[[3-[3-Fluoro-4-[4-(ethoxycar- P-126 ethanolbonyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]-methyl]-O-ethylthio-carbamate 465 (S)-N-[[3-[3-Fluoro-4-[4-(ethoxycar- P-126 isopropylbonyl)-1-piperazinyl]phenyl]-2-oxo-5- alcoholoxazolidinyl]-methyl]-O-iso-propylthio- carbamate 466(S)-N-[[3-[3,5-Difluoro-4-[4-(ethoxy- P-127 methanolcarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthio- carbamate 467(S)-N-[[3-[4-[4-(ethoxycarbonyl)-1- P-128 methanolpiperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthio-carbamate 468 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 methanolpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthiocarbamate, 469 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1-P-129 ethanol piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthio- carbamate 470(S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P-129 isopropylpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- alcoholmethyl]-O-iso-propylthiocarbamate 471(S)-N-[[3-[3,5-Difluoro-4-(4-sulfamoyl-1- P-130 methanolpiperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthio-carbamate 472 (S)-N-[[3-[4-(4-sulfamoyl-1-piperazinyl)- P-131 methanolphenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate 473(S)-N-[[3-[3-Fluoro-4-[4-(cyanomethyl)-1- P-132 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate474 (S)-N-[[3-[3,5-Difluoro-4-[4-(cyano- P-133 methanolmethyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 475(S)-N-[[3-[4-[4-(cyanomethyl)-1- P-134 methanollpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate476 (S)-N-[[3-[3-Fluoro-4-[4-(2-fluoroethyl)-1- P-135 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate477 (S)-N-[[3-[3,5-Difluoro-4-[4-(2-fluoro- P-136 methanolethyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]-methyl]-O-methylthio- carbamate 478(S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P-137 methanolpiperazinyl]phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate479 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P-138 methanolpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate480 (S)-N-[[3-[3,5-Difluro-4-(4-formyl-1- P-139 methanolpiperazinyl)phenyl]-2-oxo-5-oxazolidinyl]- methyl]-O-methylthiocarbamate481 (S)-N-[[3-[4-(4-formyl-1-piperazinyl)- P-140 methanolphenyl]-2-oxo-5-oxazolidinyl]methyl]-O- methylthiocarbamate

EXAMPLE 482(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide

[0877]

[0878] Step 1. Hexahydro-5-oxo-1,4-thiazepine is prepared according tothe procedure described by Gallego (J. Org. Chem. 1993, 58, 3905-3911).

[0879] Step 2. Lithium aluminum hydride (5.5 mL of a 1M solution in THF)is added dropwise to a stirred solution ofhexahydro-5-oxo-1,4-thiazepine (721.5 mg) in dry THF (21 mL) cooled to0° C. The reaction mixture is stirred at 0° C. for 10 min, then at roomtemperature for 4 h. The reaction mixture is quenched by carefulsuccessive addition of water (0.2 mL), 5 N aqueous NaOH (0.2 mL) andwater (0.74 mL). The reaction mixture becomes very thick and gel-like.The reaction mixture is diluted with ether (50 mL) and filtered througha pad of celite. The filter cake is washed with ether (100 mL). Thefiltrate is concentrated to afford 616.6 mg of 1,4-hexahydrothiazepinewhich is used immediately in the next step.

[0880] Step 3. To a stirred solution of 1,4-hexahydrothiazepine (596.0mg) and 3,4-difluoronitrobenzene (0.51 mL) in acetonitrile (14 mL) isadded diisopropylethylamine (1.0 mL). The yellow solution is heated atreflux for 18 h, then cooled and concentrated. The residue is dilutedwith CH₂Cl₂ (100 mL) and washed with saturated aqueous NH₄Cl (35 mL).The phases are separated and the organics are dried (MgSO₄), filteredand concentrated. The residue is purified by flash chromatography using20% EtOAc in hexane as the eluent to afford 830.2 mg of thenitrobenzene. Mp 115-116° C.; Anal. Calcd for C₁₁H₁₃FN₂O₂S: C, 51.55; H,5.11; N, 10.93; S, 12.51. Found: C, 51.47; H, 5.12; N, 10.79; S, 12.42.

[0881] Step 4. To a stirred suspension of the nitrobenzene prepared inStep 3 (5.5 g) in EtOH (260 mL) is added a solution of 2 M aqueous CuSO₄(11.9 mL). The mixture is cooled to 0° C. and NaBH₄ (4.1 g) is added inportions. The reaction mixture turns very dark and is stirred at 0° C.for 10 min, at room temperature for 30 min, and then heated at refluxfor 3 h. The cooled reaction mixture is diluted with EtOAc (500 ml) andwashed with water (200 mL). The aqueous mixture is extracted with EtOAc(3×200 mL). The combined organics are dried (MgSO₄), filtered andconcentrated to afford the aniline intermediate.

[0882] Step 5. The dark residue from Step 4 is dissolved in 2:1acetone/water (255 mL) and cooled to 0° C. To this stirred mixture isadded solid NaHCO₃ (5.4 g) followed by benzylchloroformate (7.7 mL). Thereaction mixture is stirred at 0° C. for 10 min, then at roomtemperature for 24 h. The reaction mixture is quenched with 10% aqueousNaHSO₄ (200 mL) and then poured into EtOAc (300 mL). The phases areseparated and the aqueous phase is extracted with EtOAc (2×250 mL). Thecombined organics are dried (MgSO₄), filtered and concentrated. Theresidue is purified by MPLC using 20% EtOAc in hexane to afford 6.03 gof the benzylcarbamate as a yellow solid. mp 72-74° C.; Anal. Calcd forC₁₉H₂₁FN₂O₂S: C, 63.31; H, 5.87; N, 7.77; S, 8.89. Found: C, 63.31; H,5.97; N, 7.69; S, 8.79.

[0883] Step 6. To a stirred solution of the carbamate from Step 5 (3.0g) in dry THF (33 mL) under N₂ cooled to 78° C., is added dropwise viasyringe a 1.6 M solution of nBuLi in hexane (5.4 mL). The reactionmixture was stirred at 78° C. for 35 min, then R-glycidyl butyrate (1.2mL) is added. The reaction mixture is stirred at 78° C. for 30 min, thenat room temperature overnight during which time a precipitate forms. Thereaction mixture is quenched with saturated aqueous NH₄Cl (33 mL) andpoured into EtOAc (100 mL). The phases are separated. The organic phaseis washed with saturated aqueous NaHCO₃ (50 mL), brine (50 mL), dried(MgSO₄), filtered and concentrated. The residue is purified by flashchromatography using EtOAc as the eluent to afford 2.5 g of ahydroxymethyl oxazolidinone. Mp 100-102° C. Anal. Calcd forC₁₅H₁₉FN₂O₃S: C, 55.20; H, 5.87; N, 8.58; S, 9.82. Found: C, 55.09; H,5.91; N, 8.36; S, 9.57.

[0884] Step 7. To a stirred solution of the alcohol prepared in Step 6(1.7 g) in CH₂Cl₂ (35 mL) cooled to 0° C., is added triethylamine (1.1mL) followed by methanesulfonyl chloride (0.5 mL). The reaction mixtureis stirred at 0° C. for 10 min, then at room temperature for 1 h. Thereaction mixture is treated with water (35 mL). The phases are separatedand the aqueous phase is extracted with CH₂Cl₂ (35 mL). The combinedorganic phases are dried (MgSO₄), filtered and concentrated. The residueis purified by flash chromatography using 80% EtOAc in hexane as theeluent to afford 2.1 g of the mesylate. Mp 132-142° C. Anal. Calcd forC₁₆H₂₁ FN₂O₅S₂: C, 47.51; H, 5.23; N, 6.93; S, 15.85. Found: C, 47.18;H, 5.28; N, 6.84; S, 15.60.

[0885] Step 8. Ammonia gas is bubbled into a stirred suspension of themesylate prepared in Step 7 (941.7 mg) in 1:1 THF/CH₃OH (40 mL) untilsaturated (approx. 5 min). The reaction mixture is heated in a sealedtube at 100° C. for 72 h. The cooled reaction mixture is concentrated togive the crude amine, which is immediately suspended in CH₂Cl₂ (35 mL)and cooled to 0° C. To this stirred suspension is added triethylamine(0.97 mL, 6.9 mmol) followed by di-tert-butyl dicarbonate (759.5 mg, 3.5mmol). The reaction mixture becomes homogeneous and is stirred at RT for18 h. The reaction mixture is poured into CH₂Cl₂ (75 mL) and washed withH₂O (1×50 mL). The organic phase is dried (MgSO₄), filtered andconcentrated. The resulting residue is purified on a Biotage 40 S columnusing 30-35% ethyl acetate in CH₃OH as the eluent to afford 867.4 mg ofthe protected amine. mp 74-75° C. Anal Cald: C, 56.45; H, 6.63; N, 9.88.Found: C, 56.95; H, 6.85; N, 9.55.

[0886] Step 9. To a stirred suspension of the protected amine preparedin Step 8 (205.2 mg) in 1:1 CH₃OH/H₂O (6 mL) cooled to 0° C. is addedsodium meta periodate (113.5 mg). The resulting suspension is stirred atRT for 18 h. The reaction mixture is filtered and the solid is washedwith CH₂Cl₂ (2×20 mL). The filtrate is extracted with H₂O (1×10 mL). Thephases are separated. The aqueous phase is extracted with CH₂Cl₂ (1×25mL). The combined organic phases are dried (MgSO₄), filtered andconcentrated. The white solid residue is purified on a Biotage 12 Mcolumn using 5% CH₃OH in CH₂Cl₂ as the eluent to afford 187.3 mg of thesulfoxide. mp 78-81° C.

[0887] Step 10. Dry HCl gas is passed over the surface of a stirredsolution of the sulfoxide prepared in Step 9 (179.3 mg) in CH₃OH (2 mL)cooled to 0° C. for 1 minute. The reaction mixture is stirred at 0° C.for 10 min, then at room temperature for 15 min, then concentrated. Theresulting yellow residue is suspended in THF (5 mL) and CH₂Cl₂ (5 mL)and cooled to 0° C. To this stirred suspension is added triethylamine(0.46 mL) followed by ethyldithioacetate (0.18 mL). The dark reactionmixture is stirred at RT overnight then concentrated. The dark residueis diluted with CH₂Cl₂ (30 mL) and washed with H₂O (2×15 mL). Theorganic phases are dried (MgSO₄), filtered and concentrated. The darkresidue is purified on a Biotage 12 M column using 5% CH₃OH in CH₂Cl₂ asthe eluent to afford 71.5 mg of the title compound as a tan solid. mp85-89° C.

[0888] Following the general procedure outlined in Step 10 of Example482, but substituting the dithioesters listed below, the compounds ofExamples 483 to 495 of Table K can be obtained. TABLE K ExampleDithioester No. Compound Amine (from Preparation Z) 483(5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepineS-oxide

Z(a) 484 S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiazepine S- oxide.

Z(b) 485 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide,thiazepine S- oxide.

Z(c) 486 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide, thiazepineS-oxide

Z(d) 487 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide,thiazepine S-oxide

Z(e) 488 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide,thiazepine S-oxide

Z(f) 489 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide,thiazepine S- oxide

Z(g) 490 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothio- amide,thiazepine S- oxide

Z(h) 491 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- cyclopentanecarbothio- amide,thiazepine S- oxide

Z(i) 492 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothio- amide,thiazepine S- oxide

Z(j) 493 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethio- amide,thiazepine S- oxide

Z(k) 494 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide,thiazepine S- oxide

Z(l) 495 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethio- amide,thiazepine S- oxide

Z(m)

EXAMPLE 496(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide

[0889]

[0890] The title compound can be prepared by the procedure of Example482, by substituting an appropriate quantity of2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for3,4-difluoronitrobenzene in Step 1.

[0891] Utilizing the amine prepared in Example 496, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 497 to 499 of Table L are obtained. TABLE LExample Dithioester No. Compound Amine (from Preparation Z) 497(5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepineS-oxide

Z(a) 498 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethio- amide, thiazepine S- oxide

Z(b) 499 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-cyclopropanecarbothio- amide, thiazepine S- oxide

Z(c)

EXAMPLE 500(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide

[0892]

[0893] The title compound can be prepared by the procedure of Example482, by substituting an appropriate quantity of 4-fluoronitrobenzene for3,4-difluoronitrobenzene in Step 1.

[0894] Utilizing the amine prepared in Example 500, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 501 to 503 of Table M are obtained TABLE M ExampleDithioester No. Compound Amine (from Preparation Z) 501 (5S)-N-[[3-[4-(Tetrahydro-1,4- thiazepin-4(5H)-yl))- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiazepine S-oxide

Z(a) 502 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiazepine S- oxide

Z(b) 503 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide,thiazepine S- oxide

Z(c)

EXAMPLE 504(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide

[0895]

[0896] Step 1. To a stirred solution of the thiazepine prepared in Step8 of Example 482 (243.7 mg) in 25% H₂O/acetone (8 mL) is added4methylmorpholine N-oxide (201.5 mg) followed by a solution of osmiumtetroxide in 2methyl-2-propanol (2.5 wt %, 30 μL). The reaction mixtureis stirred at room temperature for 18 h. The reaction mixture is treatedwith saturated sodium bisulfate (8 mL), then poured into CH₂Cl₂ (50 mL).The phases are separated. The aqueous phase is extracted with CH₂Cl₂(2×25 mL). The combined organic phases are washed with brine (1×25 mL),dried (MgSO₄), filtered and concentrated. The residue is purified on aBiotage 40 S column using 1% CH₃OH in CH₂Cl₂ as the eluent to afford216.1 mg (0.47 mmol, 83%) of the thiazepine S,S-dioxide as a whitesolid. mp 144-146° C.

[0897] Step 2. Dry HCl gas is passed over the surface of a stirredsolution of the thiazepine S,S-dioxide prepared in Step 1 (108.2 mg) inCH₃OH(3 mL) at 0° C. for 1 minute. The reaction mixture is stirred at 0°C. for 10 min and then at room temperature for 15 min. The reaction isconcentrated and the yellow residue is suspended in CH₂Cl₂ (2 mL) andTHF (2 mL). This stirred suspension is cooled to 0° C. and triethylamine(0.27 mL) is added followed by a solution of ethyldithioacetate (0.11mL) in THF (0.5 mL) with 0.25 mL rinse. The yellowish-green solution isstirred at 0° C. for 10 min then at room temperature for 18 h. Thereaction mixture is poured into CH₂Cl₂ (20 mL) and washed with H₂O (2×10mL). The organic phase was dried (MgSO₄), filtered and concentrated. Theresidue is purified on a Biotage 12 M column using 2% CH₃OH in CH₂Cl₂ asthe eluent to afford 77.3 mg of the title compound as a white solid. mp88-90° C.

[0898] Following the general procedure outlined in Step 2 of Example504, but substituting the dithioester listed below for ethyldithioacetate, the compounds of Examples 505 to 507 of Table N areobtained. TABLE N Example Dithioester No. Compound Amine (fromPreparation Z) 505 (5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]-phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiazepineS,S-dioxide

Z(a) 506 (5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethio- amide, thiazepine S,S-dioxide

Z(b) 507 (5S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothio- amide, thiazepine S,S-dioxide

Z(c)

EXAMPLE 508(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4-(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide

[0899]

[0900] The title compound can be prepared by the procedures of Examples504 and 482, by substituting an appropriate quantity of2,6-difluoro-4-nitrobenzene (trifluoromethane) sulfonate for3,4-difluoronitrobenzene in Step 1 of Example 482.

[0901] Utilizing the amine prepared in Example 508, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 509 to 511 of Table O are obtained. TABLE OExample Dithioester No. Compound Amine (from Preparation Z) 509(5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]- propanethioamide, thiazepine S,S-dioxide

Z(a) 510 (5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiazepine S,S- dioxide

Z(b) 511 (5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide,thiazepine S,S- dioxide

Z(c)

EXAMPLE 512(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide

[0902]

[0903] The title compound can be prepared by the procedure of Examples504 and 482, by substituting an appropriate quantity of4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1 of Example482.

[0904] Utilizing the amine prepared in Example 512, but substituting thedithioester listed below for ethyl dithioacetate in the final step, thecompounds of Examples 513 to 515 of Table P are obtained. TABLE PExample Dithioester No. Compound Amine (From Preparation Z) 513(5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo-5-oxazolidinyl]- methyl]propanethio- amide, thiazepine S,S- dioxide

Z(a) 514 (5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)-yl))phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethio- amide,thiazepine S,S- dioxide

Z(b) 515 (5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)-yl))phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide,thiazepine S,S-dioxide

Z(c)

EXAMPLE 516(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4-(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

[0905]

[0906] This compound is prepared according to the procedure of Step 8 inExample 482, but stubstituting an appropriate quantity of ethyldithioacetate for di-tert-butyl dicarbonate; mp 129-131° C.

[0907] Utilizing the amine prepared in Step 8 of Example 482, butsubstituting an appropriate quantity of the dithioester listed below fordi-tert-butyl dicarbonate, the compounds of Examples 517 to 529 of TableQ are obtained. TABLE Q Example Dithioester No. Compound Amine (FromPreparation Z) 517 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide

Z(a) 518 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide

Z(b) 519 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothio- amide

Z(c) 520 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide

Z(d) 521 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide

Z(e) 522 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide

Z(f) 523 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- 3,3-dimethylbutanethio- amide

Z(g) 524 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide

Z(h) 525 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothio- amide

Z(i) 526 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]- cylcohexanecarbothio- amide

Z(j) 527 (5S)-N-[[3-[3-5 Fluoro- 4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopropylethanethio- amide

Z(k) 528 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethio- amide

Z(l) 529 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide

Z(m)

EXAMPLE 530(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide

[0908]

[0909] This compound can be prepared according to the procedures ofExample 482 and Example 516, but substituting an appropriate quantity of2,6-difluoro-4-nitrophenyl trifluoromethane sulfonate for3,4-difluoronitrobenzene in Step 1 of Example 482.

[0910] Utilizing the amine prepared in Example 530, but substituting anappropriate quantity of the dithioester listed below for di-tert-butyldicarbonate, the compounds of Examples 531 to 533 of Table R can beprepared. TABLE R Example Dithio Compound No. Compound Amine (fromPreparation Z) 531 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide

Z(a) 532 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropanethioamide

Z(b) 533 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methyl]-yclopropanecarbothio- amide

(c)

EXAMPLE 534(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;mp 129-131° C.

[0911]

[0912] This compound can be prepared according to the procedures ofExample 482 and Example 516, but substituting an appropriate quantity of4-fluoronitrobenzene for 3,4-difluoronitrobenzene in Step 1 of Example482.

[0913] Utilizing the amine prepared in Example 534, but substituting anappropriate quantity of the dithioester listed below for di-tert-butyldicarbonate, the compounds of Examples 535 to 537 of Table S can beprepared. TABLE S Example Dithio Compound No. Compound Amine (fromPreparation Z) 535 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide

Z(a) 536 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide

Z(b) 537 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl))-phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide

Z(c)

EXAMPLE 538(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide

[0914]

[0915] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 482 for theamine 33.

[0916] By reaction of the isothiocyanate prepared in Example 538 withthe amines and alcohols listed in Table T, the compounds of Examples 539to 544 can be prepared. TABLE T Example Amine or No. CompoundIsothiocyanate Alcohol 539 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea, thiazepine S-oxide

CH₃NH₂ 540 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea,thiazepine S-oxide

(CH₃)₂NH 541 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide,thiazepine S-oxide

Azetidine 542 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S-oxide

CH₃OH 543 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S-oxide

CH₃CH₂OH 544 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate,thiazepine S-oxide

(CH₃)₂CHOH

EXAMPLE 545(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide

[0917]

[0918] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 496 for theamine 33.

[0919] By reaction of the isothiocyanate prepared in Example 545 withthe amines and alcohols listed in Table U, the compounds of Examples 546to 551 can be prepared. TABLE U Example Amine or No. CompoundIsothiocyanate Alcohol 546 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea, thiazepine S-oxide

CH₃NH₂ 547 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea,thiazepine S-oxide

(CH₃)₂NH 548 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiazepine S-oxide

Azetidine 549 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate, thiazepine S-oxide

CH₃OH 550 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S-oxide

CH₃CH₂OH 551 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S-oxide

(CH₃)₂CHOH

EXAMPLE 552(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S-oxide

[0920]

[0921] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 500 for theamine 33.

[0922] By reaction of the isothiocyanate prepared in Example 552 withthe amines and alcohols listed in Table V, the compounds of Examples 553to 558 can be prepared. TABLE V Example Amine or No. CompoundIsothiocyanate Alcohol 553 (5S)-N-[[3-[4- (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea, thiazepine S-oxide

CH₃NH₂ 554 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea,thiazepine S-oxide

(CH₃)₂NH 555 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-oxazolidinyl]methyl]-1- azetidinecarbothioamide, thiazepine S-oxide

Azetidine 556 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S-oxide

CH₃OH 557 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S-oxide

CH₃CH₂OH 558 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate,thiazepine S-oxide

(CH₃)₂CHOH

EXAMPLE 559(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide

[0923]

[0924] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 504 for theamine 33.

[0925] By reaction of the isothiocyanate prepared in Example 559 withthe amines and alcohols listed in Table W, the compounds of Examples 560to 565 can be prepared. TABLE W Example Amine or No. CompoundIsothiocyanate Alcohol 560 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 561 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea,thiazepine S,S-dioxide

(CH₃)₂NH 562 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide,thiazepine S,S-dioxide

Azetidine 563 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S,S-dioxide

CH₃OH 564 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S,S-dioxide

CH₃CH₂OH 565 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate,thiazepine S,S-dioxide

(CH₃)₂CHOH

EXAMPLE 566(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide

[0926]

[0927] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 508 for theamine 33.

[0928] By reaction of the isothiocyanate prepared in Example 566 withthe amines and alcohols listed in Table X, the compounds of Examples 561to 572 can be prepared. TABLE X Example Amine or No. CompoundIsothiocyanate Alcohol 567 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 568 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea,thiazepine S,S-dioxide

(CH₃)₂NH 569 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide, thiazepine S,S-dioxide

Azetidine 570 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate, thiazepine S,S-dioxide

CH₃OH 571 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S,S-dioxide

CH₃CH₂OH 572 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate, thiazepine S,S-dioxide

(CH₃)₂CHOH

EXAMPLE 573(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea,thiazepine S,S-dioxide

[0929]

[0930] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 512 for theamine 33.

[0931] By reaction of the isothiocyanate prepared in Example 573 withthe amines and alcohols listed in Table Y, the compounds of Examples 574to 579 can be prepared. TABLE Y Example Amine or No. CompoundIsothiocyanate Alcohol 574 (5S)-N-[[3-[4- (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea, thiazepine S,S-dioxide

CH₃NH₂ 575 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea,thiazepine S,S-dioxide

(CH₃)₂NH 576 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide,thiazepine S,S-dioxide

Azetidine 577 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate,thiazepine S,S-dioxide

CH₃OH 578 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate,thiazepine S,S-dioxide

CH₃CH₂OH 579 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate,thiazepine S,S-dioxide

(CH₃)₂CHOH

EXAMPLE 580(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0932]

[0933] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Step 8 of Example 482for the amine 33.

[0934] By reaction of the isothiocyanate prepared in Example 580 withthe amines and alcohols listed in Table Z, the compounds of Examples 581to 586 can be prepared. TABLE Z Example Amine or No. CompoundIsothiocyanate Alcohol 581 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea

CH₃NH₂ 582 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea

(CH₃)₂NH 583 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide

Azetidine 584 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate

CH₃OH 585 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate

CH₃CH₂OH 586 (5S)-N-[[3-[3-Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate

(CH₃)₂CHOH

EXAMPLE 587(5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0935]

[0936] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 530 for theamine 33.

[0937] By reaction of the isothiocyanate prepared in Example 587 withthe amines and alcohols listed in Table AA, the compounds of Examples588 to 593 can be prepared. TABLE AA Example Amine or No. CompoundIsothiocyanate Alcohol 588 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea

CH₃NH₂ 589 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea

(CH₃)₂NH 590 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1-azetidinecarbothioamide

Azetidine 591 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-methylthiocarbamate

CH₃OH 592 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro- 1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate

CH₃CH₂OH 593 (5S)-N-[[3-[3,5- Difluoro-4-(tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O-isopropylthiocarbamate

(CH₃)₂CHOH

EXAMPLE 594(5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea

[0938]

[0939] This compound can be prepared by the procedure described inExample 33, but substituting the amine prepared in Example 534 for theamine 33.

[0940] By reaction of the isothiocyanate prepared in Example 594 withthe amines and alcohols listed in Table BB, the compounds of Examples595 to 600 can be prepared. TABLE BB Example Amine or No. CompoundIsothiocyanate Alcohol 595 (5S)-N-[[3-[4- (Tetrahydro-1,4-thiazepin-4(5H)- yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-N′-methylthiourea

CH₃NH₂ 596 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]- N′,N′-dimethylthiourea

(CH₃)₂NH 597 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-1- azetidinecarbothioamide

Azetidine 598 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- methylthiocarbamate

CH₃OH 599 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- ethylthiocarbamate

CH₃CH₂OH 600 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-O- isopropylthiocarbamate

(CH₃)₂CHOH

What is claimed:
 1. A compound of the formula I

or pharmaceutical acceptable salts thereof wherein: G is

R₁ is a) H, b) NH₂, c) NH—C₁₋₄ alkyl, d) C₁₋₄ alkyl, e) —OC₁₋₄ alkyl, f)—S C₁₋₄ alkyl, g) C₁₋₄ alkyl substituted with 1-3 F, 1-2 Cl, CN or—COOC₁₋₄ alkyl, h) C₃₋₆ cycloalkyl, i) N(C₁₋₄) alkyl)₂ or j) N(CH₂)₂₋₅;A is

d) a 5-membered heteroaromatic moiety having one to three atoms selectedfrom the group consisting of S, N, and O, wherein the 5-memberedheteroaromatic moiety is bonded via a carbon atom, wherein the5-membered heteroaromatic moiety can additionally have a fused-onbenzene or naphthyl ring, wherein the heteroaromatic moiety isoptionally substituted with one to three R₄₈, e) a 6-memberedheteroaromatic moiety having at least one nitrogen atom, wherein theheteroaromatic moiety is bonded via a carbon atom, wherein the6-membered heteroaromatic moiety can additionally have a fused-onbenzene or naphthyl ring, wherein the heteroaromatic moiety isoptionally substituted with one to three R₅₅, f) a β-carbolin-3-yl, orindolizinyl bonded via the 6-membered ring, optionally substituted withone to three R₆₅,

wherein R₂ is a) H, b) F, c) Cl, d) Br, e) C₁₋₃ alkyl, f) NO₂, or g) R₂and R₃ taken together are —O—(CH₂)_(h)—O—; R is a) —S(═O)_(i) R₄, b)—S(═O)₂—N═S(O)_(j)R₅R₆, c) —SC(═O)R₇, d) —C(═O)R₈, e) —C(═O)R₉, f)—C(═O)NR₁₀R₁₁, g) —C(═NR₁₂)R₈, h) —C(R₈)(R₁₁)—OR₁₃, i) —C(R₉)(R₁₁)—OR₁₃,j) —C(R₈)(R₁₁)—OC(═O)R₁₃, k) —C(R₉)(R₁₁)—OC(═O)R₁₃, l) —NR₁₀R₁₁, m)—N(R₁₀)—C(═O)R₇, n) —N(R₁₀)—S(═O)_(i)R₇, o) —C(OR₁₄)(OR₁₅)R₈, p)—C(R₈)(R₁₆)—NR₁₀R₁₁, or q) C₁₋₈ alkyl substituted with one or more ═Oother than at alpha position, —S(═O)_(i)R₁₇, —NR₁₀R₁₁, C₂₋₅ alkenyl, orC₂₋₅ alkynyl; R₄ is a) C₁₋₄ alkyl optionally substituted with one ormore halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃, b) C₂₋₄ alkenyl, c) —NR₁₆R₁₈,d) —N₃, e) —NHC(═O)R₇, f) —NR₂₀C(═O)R₇, g) —N(R₁₉)₂, h) —NR₁₆R₁₉, or i)—NR₁₉R₂₀, R₅ and R₆ at each occurrence are the same or different and area) C₁₋₂ alkyl, or b) R₅ and R₆ taken together are —(CH₂)_(k)—; R₇ isC₁₋₄ alkyl optionally substituted with one or more halos; R₈ is a) H, orb) C₁₋₈ alkyl optionally substituted with one or more halos, or C₃₋₈cycloalkyl; R₉ is C₁₋₄ alkyl substituted with one or more a) —S(═O)R₁₇,b) —OR₁₃, c) —OC(═O)R₁₃, e) C₁₋₅ alkenyl optionally substituted withCHO; R₁₀ and R₁₁ at each occurrence are the same or different and are a)H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₂ is a) —NR₁₀R₁₁, b) —OR₁₀;or c) —NHC(═O)R₁₀; R₁₃ is a) H, or b) C₁₋₄ alkyl; R₁₄ and R₁₅ at eachoccurrence are the same or different and are a) C₁₋₄ alkyl, or b) R₁₄and R₁₅ taken together are —(CH)_(l)—; R₁₆ is a) H, b) C₁₋₄ alkyl, or c)C₃₋₈ cycloalkyl; R₁₇ is a) C₁₋₄ alkyl, or b) C₃₋₈ cycloalkyl; R₁₈ is a)H, b) C₁₋₄ alkyl, c) C₂₋₄ alkenyl, d) C₃₋₄ cycloalkyl, e) —OR₁₃ or f)—NR₂₁R₂₂; R₁₉ is a) Cl, b) Br, or c) I; R₂₀ is a physiologicallyacceptable cation; R₂₁ and R₂₂ at each occurrence are the same ordifferent and are a) H, b) C₁₋₄ alkyl, or c) —NR₂₁R₂₂ taken together are—(CH₂₎ _(m)—; wherein R₂₃ and R₂₄ at each occurrence are the same ordifferent and are a) H, b) F, c) Cl, d) C₁₋₂ alkyl, e) CN f) OH, g) C₁₋₄alkoxy, h) nitro, or i) amino; Q is

m) a diazinyl group optionally substituted with X and Y, n) a triazinylgroup optionally substituted with X and Y, o) a quinolinyl groupoptionally substituted with X and Y, p) a quinoxalinyl group optionallysubstituted with X and Y, q) a naphthyridinyl group optionallysubstituted with X and Y,

Q and R₂₄ taken together are

wherein Z¹ is a) —CH₂—, b) —CH(R¹⁰⁴)—CH₂—, c) —C(O)—, or d) —CH₂CH₂CH₂—;wherein Z² is a) —O₂S—, b) —O—, c) —N(R¹⁰⁷)—, d) —OS—, or e) —S—;wherein Z³ is a) —O₂S—, b) —O—, c) —OS—, or d) —S—; wherein A¹ is a) H—,or b) CH₃; wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e)R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl—O—C(O)—, h)HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl—O₂C— k) CH₃—C(O)—, l)CH₃—C(O)—CH₂,

A¹ and A² taken together are:

wherein R¹⁰² is a) H—, b) CH₃—, c) phenyl-CH₂— or d) CH₃C(O)—; whereinR¹⁰³ is a) (C₁-C₃)alkyl-, or b) phenyl-; wherein R¹⁰⁴ is a) H—, or b)HO—; wherein R¹⁰⁵ is a) H—, b) (C₁-C₃)alkyl-, c) CH₂═CH—CH₂—, or d)CH₃—O—(CH₂)₂—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—,d) HOCH₂—C(O)—, e) CH₃SO₂—,

g) F₂CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O)—, c) R¹⁰⁸—C(O)—,

f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)—, l)(CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂—;wherein R¹⁰⁸ is a) H—, b) (C₁-C₄)alkyl, c) aryl —(CH₂)_(p), d) ClH₂C—,e) Cl₂HC—, f) FH₂C—, g) F₂HC—, h) (C₃-C₆)cycloalkyl, or i) CNCH₂—;wherein R¹⁰⁹ is a) (C₁-C₄)alkyl, b) —CH₂Cl c) —CH₂CH═CH₂, d) aryl, or e)—CH₂CN; wherein R¹¹⁰ and R¹¹¹ are independently a) H—, b) CH₃—; orwherein R¹¹² is a) H—, b) CH₃O—CH₂O—CH₂—, or c) HOCH₂—; wherein R¹¹³ isa) CH₃—, b) HOCH₂—, c) (CH₃)₂N-phenyl, or d) (CH₃)₂N—CH₂—; wherein R¹¹⁴is a) HO—, b) CH₃O—, c) H₂N—, d) CH₃O—C(O)—O—, e)CH₃—C(O)—O—CH₂—C(O)—O—, f) phenyl-CH₂—O—CH₂—C(O)—O—, g) HO—(CH₂)₂—O—, h)CH₃O—CH₂—O—(CH₂)₂—O—, or i) CH₃O—CH₂—O—; wherein R¹¹³ is a) CH₃—, b)HOCH₂—, c) (CH₃)₂N-phenyl, or d) (CH₃)₂N—CH₂—; wherein R¹¹⁵ is a) H—, orb) Cl—; wherein R¹¹⁶ is a) HO— b) CH₃O—, or c) F; wherein R¹⁵⁰ and R¹⁵¹are each H or alkylC₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with thenitrogen atom to which each is attached form a monocyclic heterocyclicring having from 3 to 6 carbon atoms; B is an unsaturated 4-atom linkerhaving one nitrogen and three carbons; M is a) H, b) C₁₋₈ alkyl, c) C₃₋₈cycloalkyl, d) —(CH₂)_(m)OR₁₃, or e) —(CH₂)_(h)—NR₂₁R₂₂; Z is a) O, b)S, or c) NM; W is a) CH, b) N, or c) S or O when Z is NM; Y is a) H, b)F, c) Cl, d) Br, e) C₁₋₃ alkyl, or f) NO₂; X is a) H, b) —CN, c) OR₂₇,d) halo, e) NO₂, f) tetrazoyl, g) —SH, h) —S(═O)_(i)—R₄, i)—S(═O)₂—N═S(O)_(j)R₅R₆, j) —SC(═O)R₇, k) —C(═O)R₂₅, l) —C(═O)NR₂₇R₂₈, m)—C(═NR₂₉)R₂₅, n) —C(R₂₅)(R₂₈)—OR₁₃, o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃, p)—C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈, q) —NR₂₇R₂₈, r) —N(R₂₇)C(═O)R₇, s)—N(R₂₇)—S(═O)_(i)R₇, t) —C(OR₁₄)(OR₁₅)R₂₈, u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, orv) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than atalpha position, —S(═O)_(i)—R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, orC₃₋₈ cycloalkyl; R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are thesame as defined above; R₂₅ is a) H, b) C₁₋₄ alkyl optionally substitutedwith one or more halos, C₃₋₈ cycloalkyl, C₁₋₄ alkyl substituted with oneor more of —S(═O)_(i)R₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or c) C₂₋₅alkenyl optionally substituted with CHO, or CO₂R₁₃; R₂₆ is a) R₂₈, or b)NR₂₇N₂₈; R₂₇ and R₂₈ at each occurrence are the same or different andare a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, e)—(CH₂)_(h)—NR₂₁R₂₂, or f) R₂₇ and R₂₈ taken together are—(CH₂)₂O(CH₂)₂—, —(CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇); R₂₉ is a)—NR₂₇R₂₈, b) —OR₂₇, or c) —NHC(═O)R₂₈; wherein R₃₀ is a) H, b) C₁₋₈alkyl optionally substituted with one or more halos, or c) C₁₋₈ alkyloptionally substituted with one or more OH, or C₁₋₆ alkoxy, wherein E isa) NR₃₉, b) —S(═O)_(i), or c) O; R₃₈ is a) H, b) C₁₋₆ alkyl, c)—(CH₂)_(q)-aryl, or d) halo; R₃₉ is a) H, b) C₁₋₆ alkyl optionallysubstituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, d)—CO₂R₄₀, e) —COR₄₁, f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀, g) —S(═O)₂—C₁₋₆ alkyl,h) —S(═O)₂—(CH₂)_(q)-aryl, or i) —(C═O)_(j)-Het; R₄₀ is a) H, b) C₁₋₆alkyl optionally substituted with one or more OH, halo, or —CN, c)—(CH₂)_(q)-aryl, or d) —(CH₂)_(q)—OR₄₂; R₄₁ is a) C₁₋₆ alkyl optionallysubstituted with one or more OH, halo, or —CN, b) −(CH₂)_(q)-aryl, or c)—(CH₂)_(q)—OR₄₂; R₄₂ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d)—C(═O)—C₁₋₆ alkyl; aryl is a) phenyl, b) pyridyl, or c) napthyl; a to coptionally substituted with one or more halo, —CN, OH, SH, C₁₋₆ alkyl,C₁₋₆ alkoxy, or C₁₋₆ alkylthio; wherein R₄₃ is a) H, b) C₁₋₂ alkyl, c)F, or d) OH; R₄₄ is a) H, b) CF₃, c) C₁₋₃ alkyl optionally substitutedwith one or more halo, d) phenyl optionally substituted with one or morehalo, e) R₄₄ and R₄₅ taken together are a 5-, 6-, or 7-membered ring ofthe formula,

 or f) R₄₄ and R₄₅ taken together are —(CH₂)_(k)—, when R₄₆is anelectron-withdrawing group; R₄₅ and R₄₆at each occurrence are the sameor different and are a) an electron-withdrawing group, b) H, c) CF₃, d)C₁₋₃ alkyl optionally substituted with one halo, e) phenyl provided atleast one of R₄₅ or R₄₆ is an electron-withdrawing group, or f) R₄₅ andR₄₆ taken together are a 5-, 6-, 7-membered ring of the formula

U is a) CH₂, b) O, c) S, or d) NR₄₇; R₄₇ is a) H, or b) C₁₋₅ alkyl;wherein R₄₈ is a) carboxyl, b) halo, c) —CN, d) mercapto, e) formyl, f)CF₃, g) —NO₂, h) C₁₋₆ alkoxy, i) C₁₋₆ alkoxycarbonyl, j) C₁₋₆ alkythio,k) C₁₋₆ acyl, l) —NR₄₉ R₅₀, m) C₁₋₆ alkyl optionally substituted withOH, C₁₋₅ alkoxy, C₁₋₅ acyl, or —NR₄₉R₅₀, n) C₂₋₈ alkenylphenyloptionally substituted with one or two R₅₁, o) phenyl optionallysubstituted with one or two R₅₁, p) a 5-, or 6-membered (un)saturatedheterocyclic moiety having one to three atoms selected from the groupconsisting of S, N, and O, optionally substituted with one or two R₅₁,or

R₄₉ and R₅₀ at each occurrence are the same or different and are a) H,b) C₁₋₄ alkyl, c) C₅₋₆ cycloalkyl, or d) R₄₉ and R₅₀ taken together withthe nitrogen atom is a 5-, 6-membered saturated heterocyclic moietywhich optionally has a farther hetero atom selected from the groupconsisting of S, N, and O, and can in turn be optionally substitutedwith, including on the further nitrogen atom, C₁₋₃ alkyl, or C₁₋₃ acyl;R₅₁ is a) carboxyl, b) halo, c) —CN, d) mercapto, e) formyl, f) CF₃, g)—NO₂, h) C₁₋₆ alkoxy, i) C₁₋₆ alkoxycarbonyl, j) C₁₋₆ alkythio, k) C₁₋₆acyl, l) C₁₋₆ alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅acyl, or —NR₄₉R₅₀, m) phenyl, n) —C(═O)NR₅₂ R₅₃, o) —NR₄₉R₅₀, p)—N(R₅₂)(—SO₂R₅₄), q) —SO₂—NR₅₂R₅₃, or r) —S(═O)_(i)R₅₄; R₅₂ and R₅₃ ateach occurrence are the same or different and are a) H, b) C₁₋₆ alkyl,or c) phenyl; R₅₄ is a) C₁₋₄ alkyl, or b) phenyl optionally substitutedwith C₁₋₄ alkyl; wherein R₅₅ is a) carboxyl, b) halo, c) —CN, d)mercapto, e) formyl, f) CF₃, g) —NO₂, h) C₁₋₆ alkoxy, i) C₁₋₆alkoxycarbonyl, j) C₁₋₆ alkythio k) C₁₋₆ acyl, l) —NR₅₆ R₅₇, m) C₁₋₄alkyl optionally substituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, or—NR₅₆R₅₇, n) C₂₋₈ alkenylphenyl optionally substituted with one or twoR₅₈, o) phenyl optionally substituted with one or two R₅₈, p) a 5- or6-membered (un)saturated heterocyclic moiety having one to three atomsselected from the group consisting of S, N, and O, optionallysubstituted with one or two R₅₈, or

R₅₆ and R₅₇ at each occurrence are the same or different and are a) H,b) formyl, c) C₁₋₄ alkyl d) C₁₋₄ acyl, e) phenyl, f) C₃₋₆ cycloalkyl, org) R₅₆ and R₅₇ taken together with the nitrogen atom is a 5-, 6-memberedsaturated heterocyclic moiety which optionally has a further hetero atomselected from the group consisting of S, N, and O, and can in turn beoptionally substituted with, including on the further nitrogen atom,phenyl, pyrimidyl, C₁₋₃ alkyl or C₁₋₃ acyl; R₅₈ is a) carboxyl, b) halo,c) —CN, d) mercapto, e) formyl, f) CF₃, g) —NO₂, h) C₁₋₆ alkoxy, i) C₁₋₆alkoxycarbonyl, j) C₁₋₆ alkythio, k) C₁₋₆ acyl, l) phenyl, m) C₁₋₆ alkyloptionally substituted with OH, azido, C₁₋₅ alkoxy, C₁₋₅ acyl, —NR₆₅R₅₆,—SR₅₇, —O—SO₂R₆₈, or

n) —C(═O)NR₅₉ R₆₀, o) —NR₅₆R₅₇, p) —N(R₅₉)(SO₂R₅₄), q) —SO₂—NR₅₉R₆₀, r)—S(═O)_(i)—R₅₄, s) —CH═N—R₆₁, or t) —CH(OH)—SO₃R₆₄; R₅₄ is the same asdefined above; R₅₉ and R₆₀ at each occurrence are the same or differentand are a) H, b) C₁₋₆ alkyl, c) phenyl, or d) tolyl; R₆₁ is a) OH, b)benzyloxy, c) —NH—C(═O)—NH₂, d) —NH—C(═S)—NH₂, or e) —NH—C(═NH)—NR₆₂R₆₃;R₆₂ and R₆₃ at each occurrence are the same or different and are a) H,or b) C₁₋₄ alkyl optionally substituted with phenyl or pyridyl; R₆₄ isa) H, or b) a sodium ion; R₆₅ and R₆₆ at each occurrence are the same ordifferent and are a) H, b) formyl, c) C₁₋₄ alkyl, d) C₁₋₄ acyl, e)phenyl, f) C₃₋₆ cycloalkyl, g) R₆₅ and R₆₆ taken together are a 5-,6-membered saturated heterocyclic moiety having one to three atomsselected from the group consisting of S, N, and O, optionallysubstituted with, including on the nitrogen atom, phenyl, pyrimidyl,C₁₋₃ alkyl, or C₁₋₃ acyl, h) —P(O)(OR₇₀)(OR₇₁), or i) —SO₂—R₇₂; R₆₇ is

R₆₈ is C₁₋₃ alkyl; R₆₉ is a) C₁₋₆ alkoxycarbonyl, or b) carboxyl; R₇₀and R₇₁ at each occurrence are the same or different and are a) H, or b)C₁₋₃ alkyl; R₇₂ is a) methyl, b) phenyl, or c) tolyl; wherein K is a) O,or b) S; R₇₃, R₇₄, R₇₅, R₇₆, and R₇₇ at each occurrence are the same ordifferent and are a) H, b) carboxyl, c) halo, d) —CN, e) mercapto, f)formyl, g) CF₃, h) —NO₂, i) C₁₋₆ alkoxy, j) C₁₋₆ alkoxycarbonyl, k) C₁₋₆alkythio, l) C₁₋₆ acyl, m) —NR₇₈ R₇₉, n) C₁₋₆ alkyl optionallysubstituted with OH, C₁₋₅ alkoxy, C₁₋₅ acyl, —NR₇₈R₇₉,—N(phenyl)(CH₂—CH₂—OH), —O—CH(CH₃)(OCH₂CH₃), or—O-phenyl-[para-NHC(═O)CH₃], o) C₂₋₈ alkenylphenyl optionallysubstituted with R₅₁, p) phenyl optionally substituted with R₅₁, or q) a5-, or 6-membered (un)saturated heterocyclic moiety having one to threeatoms selected from the group consisting of S, N, and O, optionallysubstituted with R₅₁; R₅₁ is the same as defined above; R₇₈ and R₇₉ ateach occurrence are the same or different and are a) H, b) C₁₋₄ alkyl,c) phenyl, or d) R₇₈ and R₇₉ taken together with the nitrogen atom is a5-, 6-membered saturated heterocyclic moiety which optionally has afurther hetero atom selected from the group consisting of S, N, and O,and can in turn be optionally substituted with, including on thenitrogen atom, C₁₋₃ alkyl, or C₁₋₃ acyl; further wherein T is a) O, b)S, or c) SO₂; R₇₅, R₇₆, and R₇₇ are the same as defined above; R₈₀ is a)H, b) formyl, c) carboxyl, d) C₁₋₆ alkoxycarbonyl, e) C₁₋₈ alkyl, f)C₂₋₈ alkenyl, wherein the substituents (e) and (f) can be optionallysubstituted with OH, halo, C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆ alkylthio orC₁₋₆ alkoxycarbonyl, or phenyl optionally substituted with halo, g) anaromatic moiety having 6 to 10 carbon atoms optionally substituted withcarboxyl, halo, —CN, formyl, CF₃, —NO₂, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆acyl, C₁₋₆ alkylthio, or C₁₋₆ alkoxycarbonyl; h) —NR₈₁R₈₂, i) —OR₉₀, j)—S(═O)_(i)—R₉₁, k) —SO₂—N(R₉₂)(R₉₃), or l) a radical of the followingformulas: R₈₁ and R₈₂ at each occurrence are the same or different andare a) H, b) C₃₋₆ cycloalkyl, c) phenyl, d) C₁₋₆ acyl, e) C₁₋₈ alkyloptionally substituted with OH, C₁₋₆ alkoxy which can be substitutedwith OH, a 5-, or 6-membered aromatic heterocyclic moiety having one tothree atoms selected from the group consisting of S, N, and O, phenyloptionally substituted with OH, CF₃, halo, —NO₂, C₁₋₄alkoxy, —NR₈₃R₈₄,or

V is a) O, b) CH₂, or c) NR₈₇; R₈₃ and R₈₄ at each occurrence are thesame or different and are a) H, or b) C₁₋₄ alkyl; R₈₅ is a) OH, b) C₁₋₄alkoxy, or c) —NR₈₈ R₈₉; R₈₆ is a) H, or b) C₁₋₇ alkyl optionallysubstituted with indolyl, OH, mercaptyl, imidazoly, methylthio, amino,phenyl optionally substituted with OH, —C(═O)—NH₂, —CO₂H, or—C(═NH)—NH₂; R₈₇ is a) H, b) phenyl, or c) C₁₋₆ alkyl optionallysubstituted by OH; R₈₈ and R₈₉ at each occurrence are the same ordifferent and are a) H, b) C₁₋₆ alkyl c) C₁₋₆ cycloalky, or d) phenyl;R₉₀ is a) C₁₋₈ alkyl optionally substituted with C₁₋₆ alkoxy or C₁₋₆hydroxy, C₃₋₆ cycloalkyl, a 6-membered aromatic optionally benzo-fusedheterocyclic moiety having one to three nitrogen atoms, which can inturn be substituted with one or two —NO₂, CF₃, halo, —CN, OH, C₁₋₅alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl;

c) phenyl, or d) pyridyl; R₉₁ is a) C₁₋₁₆ alkyl, b) C₂₋₁₆ alkenyl, wherein the substituents (a) and (b) can be optionally substituted withC₁₋₆ alkoxycarbonyl, or a 5-, 6-, 7-membered aromatic heterocyclicmoiety having one to three atoms selected from the group consisting ofS, N, and O, c) an aromatic moiety having 6 to 10 carbon atoms, or d) a5-, 6-, 7-membered aromatic heterocyclic moiety having one to threeatoms selected from the group consisting of S. N, and O,  wherein thesubstituents (c) and (d) can be optionally substituted with carboxyl,halo, —CN, formyl, CF₃, —NO₂, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ acyl, C₁₋₆alkylthio, or C₁₋₆ alkoxycarbonyl; R₉₂ and R₉₃ at each occurrence arethe same or different and are a) H, b) phenyl, c) C₁₋₆ alkyl, or d)benzyl; R₉₄ and R₉₅ at each occurrence are the same or different and area) H, b) OH, c) C₁₋₆ alkyl optionally substituted with —NR₈₃ R₈₄, or d)R₉₄ and R₉₅ taken together are ═O; R₉₆ is a) an aromatic moiety having 6to 10 carbon atoms, b) a 5-, or 6-membered aromatic optionallybenzo-fused heterocyclic moiety having one to three atoms selected fromthe group consisting of S, N, and O,  wherein the substituents (a) and(b) which can in turn be substituted with one or three —NO₂, CF₃, halo,—CN, OH, phenyl, C₁₋₅ alkyl, C₁₋₅ alkoxy, or C₁₋₅ acyl, c) morpholinyl,d) OH, e) C₁₋₆ alkoxy, f) —NR₈₃R₈₄, g) —C(═O)—R₉₇, or

R₉₇ is a) morpholinyl, b) OH, or c) C₁₋₆ alkoxy; h is 1, 2, or 3; i is0, 1, or 2; j is 0 or 1; k is 3, 4, or 5; l is 2 or 3; m is 4 or 5; n is0, 1, 2, 3, 4, or 5; p is 0, 1, 2, 3, 4, or 5; with the proviso that nand p together are 1, 2, 3, 4, or 5; q is 1, 2, 3, or 4; r is 2, 3, or4; t is 0, 1, 2, 3, 4, 5, or 6; u is 1 or 2; w is 0, 1, 2, or
 3. 2. Acompound of claim 1 which is: a)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;b)(S)-N-[[3-[3-Fluoro-4-[4-(5-methyl1,3,4-thiadiazol2-yl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;c)(S)-N-[[3-[3-Fluoro-4-[2′,6′-dioxospiro[piperidine-4,4′-imidazolidine]1-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;d)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;e)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;f)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′-methylthiourea;g)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-thioformamide;h)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thiopropion-amide;i)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-chlorothioacetamide;j)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α,α-trifluorothioacetamide;k)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-fluorothioacetamide;l)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-difluorothioacetamide;m)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-cyanothioacetamide;n)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α-dichlorothioacetamide;o)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α-(methoxycarbonyl)thioacetamide;p)(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;q)(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;r))(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;s)(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;t)(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide;u)(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiomorpholine S-oxide; v)(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio-acetamide,thiomorpholine S, S-dioxide; w)(S)-N-[[3-[3,5-Difluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;x)(S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;y)(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;z)(S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2-oxo-5-oxazolidinyl]methyl]thiourea;aa)(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methylthiourea,thiomorpholine S-oxide; bb)(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-S-methyldithiocarbamate;3. A compound of claim 1 which is(S)-trans-N-[[3-[3-fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide.4. A compound of claim 1 which is(S)-N-[[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiomorpholine S-oxide.
 5. A method for treating microbial infections inpatients comprising administering to a patient in need thereof aneffective amount of a compound of Formula I.
 6. A compound of claim 1wherein G is


7. A compound of claim 1 wherein A is


8. A compound of claim 7 wherein Q is


9. A compound of claim 1 wherein G is


10. A compound of claim 9 wherein Z² is —O₂S—.
 11. A compound of claim10 which is(5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S,S-dioxide.
 12. A compound of claim 9 wherein Z² is —OS—.13. A compound of claim 12 which is(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide,thiomorpholine S-oxide;(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide,thiomorpholine S-oxide;(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothio-amide,thiomorpholine S-oxide;(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-methylthiocarbamate,thiomorpholine S-oxide;(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate,thiomorpholine S-oxide;(S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-isopropylthiocarbamate,thiomorpholine S-oxide;(5S)-N-[[3-[3-Fluoro-4-tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide,thiazepine S-oxide,(5S)-N-[[3-[3-Fluoro-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-N′,N′-dimethylthiourea,thiomorpholine S-oxide, or(5S)-N-[[3-[3-Fluoro-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide,thiomorpholine S-oxide.
 14. A compound of claim 9 wherein Z² is O.
 15. Acompound of claim 14 which is(S)-N-[[3-[3-Fluoro-4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-O-ethylthiocarbamate;(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;(S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropane-carbothioamide16. A compound of claim 9 wherein Z² is —S—.
 17. A compound of claim 9which is(5S)-N-[[3-[4-(tetrahydro-1,4-thiazepine-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide.18. A compound of claim 9 wherein Z² is —N(R¹⁰⁷)—.
 19. A compound ofclaim 16 which is(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl-2-oxo-5-oxazolidinyl]methyl]propanethiomide;(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;(S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;(S)-N-[[3-[3-Fluoro-4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide;(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;(S)-N-[[3-[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;(S)-N-[[3-[3-Fluoro-4-[4-(methanesulfonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide;(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanethioamide;(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2-methylpropanethioamide;(S)-N-[[3-[3-Fluoro-4-(4-formyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]cyclopropanecarbothioamide;or(S)-N-[[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide.